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Smooth Muscle Cells (smooth + muscle_cell)
Kinds of Smooth Muscle Cells Terms modified by Smooth Muscle Cells Selected AbstractsPARATHYROID HORMONE HAS A PROSCLEROTIC EFFECT ON VASCULAR SMOOTH MUSCLE CELLSNEPHROLOGY, Issue 1 2002Vlado Perkovic [source] PIOGLITAZONE INHIBITS HOMOCYSTEINE-INDUCED MIGRATION OF VASCULAR SMOOTH MUSCLE CELLS THROUGH A PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR ,-INDEPENDENT MECHANISMCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 12 2008Li Li SUMMARY 1Peroxisome proliferator-activated receptor (PPAR)-, agonists have been demonstrated to exert protective effects against homocysteine (Hcy)-induced pathogenesis. However, the effects of PPAR-, agonists on Hcy-induced migration are unknown. In the present study, we examined the effect of pioglitazone on the migration of vascular smooth muscle cells (VSMC) induced by Hcy and the possible mechanism involved. 2Vascular smooth muscle cells were isolated from the thoracic aortas of male Sprague-Dawley rats. The migration of VSMC was examined using a transwell technique. The generation of intracellular reactive oxygen species (ROS) was measured using the ROS-sensitive fluoroprobe 2,,7,-dichlorodihydrofluorescein diacetate. The activity of NAD(P)H oxidase was assessed by lucigenin enhanced chemiluminescence. Activation of p38 mitogen-activated protein kinase (MAPK) was determined by western blotting. 3The results showed that pioglitazone dose-dependently inhibited the migration of VSMC induced by Hcy. This was not reversed by the PPAR-, antagonist GW9662. In addition, pretreatment with the NAD(P)H oxidase inhibitor diphenylene iodonium (DPI), the free radical scavenger N -acetylcysteine and the p38 MAPK inhibitor SB202190 blocked Hcy-induced VSMC migration. Furthermore, we observed that pioglitazone suppressed Hcy-induced intracellular ROS production; similar effects were observed with DPI and NAC. Pioglitazone attenuated Hcy-induced activation of NAD(P)H oxidase. Moreover, pioglitazone blocked Hcy-induced p38 MAPK phosphorylation; similar effects were observed for DPI, NAC and SB202190. 4The data demonstrate that pioglitazone inhibits Hcy-induced VSMC migration that is independent of PPAR-,. Furthermore, part of the biological effect of pioglitazone involves a decrease in the levels of NAD(P)H oxidase derived-ROS and p38 MAPK activation. [source] STIMULATION OF OESTROGEN RECEPTOR-EXPRESSING ENDOTHELIAL CELLS WITH OESTROGEN REDUCES PROLIFERATION OF COCULTURED VASCULAR SMOOTH MUSCLE CELLSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 3 2008Malin Odenlund SUMMARY 1Oestrogen reduces vascular smooth muscle cell proliferation in mouse vascular injury models. Data on the antiproliferative effect of oestrogen in cultured vascular smooth muscle cells (VSMC) are less conclusive than those obtained in whole animal studies. 2In the present study, we investigated the hypothesis that oestrogen-induced attenuation of VSMC proliferation is facilitated by the presence of endothelial cells (EC) using a coculture system of EC and VSMC. 3Treatment with a physiological concentration of oestrogen (17,-estradiol (E2); 100 nmol/L) had no effect on fetal calf serum (FCS)-stimulated DNA synthesis in either A7r5 VSMC or bEnd.3 EC. However, stimulation of bEnd. 3 cells with E2 in a coculture system of bEnd.3 and A7r5 cells reduced FCS-induced DNA synthesis in A7r5 cells by approximately 45%. The nitric oxide synthase inhibitor NG -nitro- l- arginine methyl ester (l -NAME; 100 µmol/L) did not reverse the oestrogen-induced attenuation of DNA synthesis. The antiproliferative effect of E2 may be mediated via either oestrogen receptor (ER) ,, ER, or both because the bEnd.3 cells expressed immunoreactivity for both ER subtypes. 4These data show that ER,- and ER,-expressing endothelial cells, which are stimulated with a physiological concentration of oestrogen, release a factor(s) that arrests the proliferation of cocultured VSMC. Oestrogen-induced attenuation of vascular smooth muscle cell proliferation is not prevented by l -NAME, suggesting that a mechanism other than endothelial NO is involved. [source] EARLY ACTIVATION OF INTERNAL MEDIAL SMOOTH MUSCLE CELLS IN THE RABBIT AORTA AFTER MECHANICAL INJURY: RELATIONSHIP WITH INTIMAL THICKENING AND PHARMACOLOGICAL APPLICATIONSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 1-2 2006Huguette Louis SUMMARY 1Smooth muscle cells (SMC) participate in both inflammatory and dedifferentiation processes during atherosclerosis, as well as during mechanical injury following angioplasty. In the latter, we studied medial SMC differentiation and inflammation processes implicated early after de-endothelialization in relation to mechanical stresses. We hypothesized that activation of a subpopulation of SMC within the media plays a crucial role in the early phase of neointimal formation. 2For this purpose, we used a rabbit model of balloon injury to study activation and differentiation of medial SMC in the early time after denudation and just before neointima thickening. Inflammation was evaluated by the expression of vascular cell adhesion molecule (VCAM)-1, integrin a4b1 and nuclear factor (NF)-kB. Myosin isoforms and 2P1A2 antigen, a membrane protein expressed by rabbit dedifferentiated SMC, were used as markers of differentiation. 3On day 2 after de-endothelialization, VCAM-1, a4b1 and NF-kB were coexpressed by a well-defined subpopulation of SMC of the internal part of the media, in the vicinity of the blood stream. At the same time, the majority of SMC throughout the media expressed non-muscle myosin heavy chain-B (nm-MHC-B) and 2P1A2 antigen. On day 7, when intimal thickening appeared, SMC of the media were no longer activated, whereas some intimal SMC expressed the activation markers. Thus, after de-endothelialization, early dedifferentiation occurs in most of the medial SMC, whereas activation concerned only a subpopulation of SMC located in the internal media. Using the T-type voltage-operated calcium channel blocker mibefradil (0.1,1 mmol/L) in SMC culture, we showed that this agent exhibited an antiproliferative effect in a dose-dependant manner only on undifferentiated cells. 4In conclusion, the results suggest that the activated SMC represent cells that are potentially able to migrate and participate in the intimal thickening process. Thus, the medial SMC inflammatory process, without any contribution of inflammatory cells, may represent a major mechanism underlying the development of intimal thickening following mechanical stress. In humans, inhibition of T-type calcium channels may be a tool to prevent the early proliferation step leading to neointimal formation. [source] Aging Increases the Interleukin-1,,Induced INOS Gene Expression and Nitric Oxide (NO) Production in Vascular Smooth Muscle CellsJOURNAL OF CARDIAC SURGERY, Issue 6 2002Gabriel HH Chan Objectives: Inducible form of nitric oxide synthase (iNOS) is induced by cytokines (e.g. interleukin-1, (IL-1,)) during pathological conditions, such as sepsis. Excessive NO synthesis in blood vessels during sepsis can result in massive vasodilation and life-threatening hypotension. In addition, chronic expression of iNOS contributes to onset of diabetes, autoimmune diseases, arthritis, renal toxicity, and neurodegenerative disorders. The purpose of the present study was to examine the effect of aging on the levels of expression of iNOS induced by a low concentration (5 ng/ml) of IL-1, in VSMCs. Methods: Gene expression of iNOS was determined by RT-PCR and analysis of the PCR products by both agarose gel electrophoresis and capillary electrophoresis with laser-induced fluorescence detector (CE-LIF). This new CE-LIF technique, just developed in our laboratory, provides greater than 1,000 fold better sensitivity compared to agarose gels. The production of nitrite, the stable metabolite of NO, was measured (by a modified Griess reaction) in the media of cultured VSMCs isolated from young and elderly rats (3-month and 20-months old, respectively) of both genders following the exposure to IL-1, (5 ng/ml). VSMCs were used in their 1st passage to avoid phenotypic changes that typically occur in cultures of VSMCs after 3-10 passages. Results: IL-1, (5 ng/ml) caused a much larger increase in iNOS mRNA in VSMCs of elderly rats as compared to young rats. Furthermore, IL-1, (5 ng/ml) had no significant effect on nitrite levels in VSMCs of young, but significantly increased nitrite levels by 7.9 fold in VSMCs from elderly male rats and by 2.6 fold in VSMCs from elderly female rats, as compared to young rats. A report had previously shown that the neuropeptide CGRP could synergistically enhance the expression of iNOS caused by IL-1, in later passages (10-15 passages) of rat aortic VSMCs (i.e. phenotypically modulated VSMCs). We found that IL-1, and CGRP together did not act synergistically to increase production of nitrite in our phenotypically normal (1st passage) VSMCs. Conclusion: IL-1,, at a low concentration (5 ng/ml), preferentially induces iNOS expression and increases production of NO in VSMCs of elderly rats as compared to young rats. The data suggest that aging enhances the responsiveness of VSMCs to the iNOS-inducing actions of the cytokine IL-1,. This may be a contributing factor in the increased risk of developing severe hypotension in elderly patients with sepsis. (Supported by a Direct Grant for Research). [source] Behavior of Nonselective Cation Channels and Large-Conductance Ca2+ -Activated K+ Channels Induced by Dynamic Changes in Membrane Stretch in Cultured Smooth Muscle Cells of Human Coronary ArteryJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 1 2003PH.D., SHENG-NAN WU M.D. Stretch-Activated Ion Channels. Introduction: The effects of membrane stretch on ion channels were investigated in cultured smooth muscle cells of human coronary artery. Methods and Results: In the cell-attached configuration, membrane stretch with negative pressure induced two types of stretch-activated (SA) ion channels: a nonselective cation channel and a large-conductance Ca2+ -activated K+ (BKCa) channel. The single-channel conductances of SA cation and BKCa channels were 26 and 203 pS, respectively. To elucidate the mechanism of activation of these SA channels and to minimize mechanical disruption, a sinusoidal change in pipette pressure was applied to the on-cell membrane patch. During dynamic changes in pipette pressure, increases in SA cation channel activity was found to coincide with increases in BKCa channel activity. In the continued presence of cyclic stretch, the activity of SA cation channels gradually diminished. However, after termination of cyclic stretch, BKCa channel activity was greatly enhanced, but the activity of SA cation channels disappeared. Conclusion: This study is the first to demonstrate that the behavior of SA cation and BKCa channels in coronary smooth muscle cells is differentially susceptible to dynamic changes in membrane tension. [source] ATP-Sensitive K+ Channels of Vascular Smooth Muscle CellsJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 1 2003WILLIAM C. COLE Ph.D. ATP-sensitive potassium channels (KATP) of vascular smooth muscle cells represent potential therapeutic targets for control of abnormal vascular contractility. The biophysical properties, regulation and pharmacology of these channels have received intense scrutiny during the past twenty years, however, the molecular basis of vascular KATP channels remains ill-defined. This review summarizes the recent advancements made in our understanding of the molecular composition of vascular KATP channels with a focus on the evidence that hetero-octameric complexes of Kir6.1 and SUR2B subunits constitute the vascular KATP subtype responsible for control of arterial diameter by vasoactive agonists. [source] Cellular Physiology of Retinal and Choroidal Arteriolar Smooth Muscle CellsMICROCIRCULATION, Issue 1 2007C. N. SCHOLFIELD ABSTRACT Control of ocular blood flow occurs predominantly at the level of the retinal and choroidal arterioles. The present article provides an overview of the Ca2 + handling mechanisms and plasmalemmal ion channels involved in the regulation of retinal and choroidal arteriolar smooth muscle tone. Increases in global intracellular free Ca2 + ([Ca2 +]i) involve multiple mechanisms, including agonist-dependent release of Ca2 + from intracellular stores through activation of the inositol trisphosphate (IP3) pathway. Ca2 + enters by voltage-dependent L-type Ca2 + channels and novel dihydropyridine-sensitive store-operated nonselective cation channels. Ca2 + extrusion is mediated by plasmalemmal Ca2 + -ATPases and through Na+/Ca2+ exchange. Local Ca2 + transients (Ca2 + sparks) play an important excitatory role, acting as the building blocks for more global Ca2 + signals that can initiate vasoconstriction. K+ and Cl, channels may also affect cell function by modulating membrane potential. The precise contribution of each of these mechanisms to the regulation of retinal and choroidal perfusion in vivo warrants future investigation. [source] Prostaglandin F2, Stimulates Endothelial Nitric Oxide Synthase Depending on the Existence of Bovine Granulosa Cells: Analysis by Co-culture System of Endothelial Cells, Smooth Muscle Cells and Granulosa CellsREPRODUCTION IN DOMESTIC ANIMALS, Issue 5 2008K Shirasuna Contents Prostaglandin F2, (PGF2,) induces luteolysis in the mid but not in the early luteal phase; despite this, both the early and the mid corpus luteum (CL) have PGF2, receptor (FPr). We previously indicated that the luteal blood flow surrounding the CL drastically increases prior to a decrease of progesterone (P) in the cows, suggesting that an acute increase of luteal blood flow may be an early sign of luteolysis in response to PGF2, and that this may be induced by a vasorelaxant nitric oxide (NO). The aim of this study was to investigate the luteal stage-dependent and the site-restricted effect of PGF2, and NO on the mRNA expressions and P secretion. To mimic the local luteal region both of peripheral and central areas of the CL, we utilized co-cultures using bovine aorta endothelial cells (EC), smooth muscle cells (SMC) and luteinizing granulosa cells (GC) or fully-luteinized GC. PGF2, stimulated the expression of endothelial NO synthase (eNOS) mRNA at 0.5 h in mix-cultures of EC and SMC with fully-luteinized GC but not with luteinizing GC. The expression of eNOS mRNA in EC was increased by PGF2, at 1 h only when EC was cultured together with fully-luteinized GC but not with luteinizing GC. In all co-cultures, PGF2, did not affect the mRNA expression of FPr. Treatment of NO donor inhibited P secretion at 0.5 h. In conclusion, the present study suggests that the coexistence of the mature luteal cells (fully-luteinized GC) with EC/SMC may be crucial for acquiring functional NO synthesis induced by PGF2,. [source] Effect of Testosterone on Potassium Channel Opening in Human Corporal Smooth Muscle CellsTHE JOURNAL OF SEXUAL MEDICINE, Issue 4 2008Deok Hyun Han MD ABSTRACT Introduction., In humans, the role of testosterone in sexual functions, including sexual desire, nocturnal penile erections, and ejaculatory volume, has been relatively well established. However, the effects of testosterone on intrapenile structure in humans remains controversial. Aim., We assessed the direct effects of testosterone on potassium channels in human corporal smooth muscle cells, in an effort to understand the mechanisms inherent to the testosterone-induced relaxation of corporal smooth muscle cells at the cellular and molecular levels. Methods., We conducted electrophysiologic studies using cultured human corporal smooth muscle cells. We evaluated the effects of testosterone on potassium channels,BKCa and KATP channels,by determining the whole-cell currents and single-channel activities. For the electrophysiologic recordings, whole-cell and cell-attached configuration patch-clamp techniques were utilized. Main Outcome Measures., Changes in whole-cell currents and channel activities of BKCa and KATP channels by testosterone. Results., Testosterone (200 nM) significantly increased the single-channel activity of calcium-activated potassium (BKCa) channels and whole-cell K+ currents by 443.4 ± 83.4% (at +60 mV; N = 11, P < 0.05), and this effect was abolished by tetraethylammonium (TEA) (1 mM), a BKCa channel blocker. The whole-cell inward K+ currents of the KATP channels were also increased by 226.5 ± 49.3% (at ,100 mV; N = 7, P < 0.05). In the presence of a combination of vardenafil (10 nM) and testosterone (200 nM), the BKCa channel was activated to a significantly higher degree than was induced by testosterone alone. Conclusions., The results of patch-clamp studies provided direct molecular evidence that testosterone stimulates the activity of BKCa channels and KATP channels. An understanding of the signaling mechanisms that couple testosterone receptor activation to potassium channel stimulation will provide us with an insight into the cellular processes underlying the vasorelaxant effects of testosterone. Han DH, Chae MR, Jung JH, So I, Park JK, and Lee SW. Effect of testosterone on potassium channel opening in human corporal smooth muscle cells. J Sex Med 2008;5:822,832. [source] (-)-Epigallocatechin Gallate Inhibits Endothelin-1-Induced C-Reactive Protein Production in Vascular Smooth Muscle CellsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2010Chen-Jing Wang Based on our previous study, the effect of EGCG on endothelin-1 (ET-1)-induced CRP production in rat vascular smooth muscle cells (VSMCs) and the possible mechanism were observed. The in vitro experiments showed that EGCG concentration-dependently inhibited ET-1-stimulated expression of CRP both in protein and mRNA levels in VSMCs as determined by the immunocytochemical staining, the enzyme-linked immunosorbent assay and the real-time quantitative polymerase chain reaction (RT-qPCR). The in vivo investigation with the double-labelled immunofluorescence staining and RT-qPCR displayed that EGCG also prevented ET-1-induced CRP expression in protein and mRNA levels in the aortic VSMCs of rats receiving the subchronic infusion of ET-1. In addition, EGCG suppressed reactive oxygen species (ROS) generation evoked by ET-1 in VSMCs as observed by the fluorescence probe. These demonstrate that EGCG may inhibit ET-1-stimulated generation of CRP in VSMCs so to relieve the inflammatory response and oxidative stress via blocking ROS signal, which provides new evidence for an anti-atherosclerotic effect of EGCG. [source] Atorvastatin Decreases C-Reactive Protein-Induced Inflammatory Response in Pulmonary Artery Smooth Muscle Cells by Inhibiting Nuclear Factor-,B PathwayCARDIOVASCULAR THERAPEUTICS, Issue 1 2010Jie Li C-reactive protein (CRP) is well-known inflammatory marker, and recognized as a risk predictor of pulmonary arterial diseases. Although statins have a beneficial effect in animal models and patients with pulmonary arterial hypertension (PAH), the underlying mechanisms of their actions have less been investigated. The aims of this study was to examined the effects of CRP on expressions of interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1), and the possible mechanisms of atorvastatin on CRP-induced IL-6 and MCP-1 production in cultured human pulmonary artery smooth muscle cells (PASMCs). In a preliminary study, the human PASMCs were stimulated by a variety of concentrations of CRP (5,200 ,g/mL) at different time points (0, 3, 6, 9, 12, 18 and 24 h) for the purpose of determining the dose- and time-dependent effects of CRP on inflammatory response of the cells. Then, the cells were pre-incubated for 2 h with atorvastatin (0.1,10 ,mol/L) in the presence of CRP. The supernatant levels of both IL-6 and MCP-1 secretion were examined by ELISA. The cellular mRNA expressions of IL-6 and MCP-1 and nuclear factor-,B (NF-,B) activity were determined by real-time reverse transcription and polymerase chain reaction (RT-PCR) and electrophoretic mobility shift assay (EMSA), respectively. CRP resulted in elevated IL-6 and MCP-1 secretion and mRNA expression in a dose- and time-dependent manner. In addition, CRP also significantly activated the NF-,B pathway. Preincubation with 0.1,10 ,mol/L of atorvastatin significantly decreased the secretions of IL-6 and MCP-1 induced by CRP. Moreover, 10 ,mol/L of atorvastatin completely abrogated CRP-induced increase in IL-6 and MCP-1 by attenuating the activation of NF-,B. The present study demonstrated that inhibiting effect of atorvastatin on CRP-induced inflammatory response in cultured PASMCs was associated with NF-,B pathway. This pathway might represent a promising target for controlling CRP-induced inflammatory response in pulmonary arterial diseases. [source] Altered Mitogen-Activated Protein Kinase Activation In Vascular Smooth Muscle Cells From Spontaneously Hypertensive RatsCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2002Takao Kubo SUMMARY 1.,We previously reported that activation function of mitogen-activated protein kinases (MAPK) is enhanced in aorta strips from both prehypertensive and hypertensive spontaneously hypertensive rats (SHR) and that this enhancement of MAPK activation results from enhanced MAPK activation reactivity to angiotensin (Ang) II in SHR aorta strips. 2.,The purpose of the present study was to examine whether the enhanced function of the vascular angiotensin system observed in SHR aorta strips results from genetic alterations of vascular smooth muscle cells from SHR. 3.,Basal MAPK activity was within normal limits in cells from 4-week-old SHR, whereas enzyme activity was enhanced in 9-week-old SHR compared with age-matched Wistar-Kyoto (WKY) rats. 4.,Mitogen-activated protein kinase activation reactivity to AngII and endothelin-1 was enhanced in 9-week-old SHR cells but not in 4-week-old SHR cells. The enhancement of basal MAPK activity in 9-week-old SHR cells was abolished by a combination of the angiotensin AT1 receptor antagonist losartan and the endothelin receptor antagonist BQ123. 5.,These findings suggest that MAPK activation function in 4-week-old SHR cells is not enhanced. Thus, it appears that factors outside vascular smooth muscle cells are needed for the enhanced MAPK activation observed in 4-week-old SHR aorta strips. In 9-week-old SHR, MAPK activation function is enhanced in cells themselves and this function may, at least in part, contribute to the enhanced MAPK activation observed in SHR aorta strips. [source] Effects of local delivery of trapidil on neointima formation in a rabbit angioplasty modelBRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2000Kai Zacharowski Smooth muscle cell (SMC) proliferation can result in luminal reduction of a vessel following balloon angioplasty. This study was designed (i) to determine if local administration of trapidil (triazolopyrimidine) into a vessel wall reduces neointima formation, and (ii) to explore the mechanism involved in the subsequent reduction in cell proliferation. Following balloon angioplasty in 40 anaesthetized New Zealand White rabbits, trapidil (50,200 mg) or its vehicle (saline) was injected into the dilated vessel wall of the right femoral artery. Experimental groups and time of investigation: (I) vehicle (2 weeks, n=3), (II) trapidil-100 mg (2 weeks, n=3), (III) vehicle (3 weeks, n=8), (IV) trapidil-50 mg (3 weeks, n=5); (V) trapidil-100 mg (3 weeks, n=9) or (V) trapidil-200 mg (3 weeks, n=7). After 2 weeks, there was a significant reduction of intimal hyperplasia (expressed as intima to media area ratio) in the trapidil group compared with vehicle (0.44±0.04 vs 0.93±0.04, *P<0.05) and also a significant reduction in cell proliferation (% ratio of BrdU-positive cells to total cell number: vehicle 14±2% vs trapidil 6±1%, *P<0.05). After 3 weeks, there was a dose-dependent reduction of intimal hyperplasia in the trapidil groups compared with vehicle (trapidil 50 mg 1.14±0.04; trapidil 100 mg 0.91±0.09*; trapidil 200 mg 0.77±0.09* vs vehicle 1.67±0.23, *P<0.05). Thus, the local administration of trapidil to the rabbit femoral artery reduces the neointima formation, which occurs 2 or 3 weeks after balloon angioplasty via a mechanism, which is dependent on inhibition of cell proliferation. British Journal of Pharmacology (2000) 129, 566,572; doi:10.1038/sj.bjp.0703098 [source] Vascular smooth muscle cell phenotypic modulation in culture is associated with reorganisation of contractile and cytoskeletal proteinsCYTOSKELETON, Issue 3 2001Nathalie F. Worth Abstract Smooth muscle cells (SMC) exhibit a functional plasticity, modulating from the mature phenotype in which the primary function is contraction, to a less differentiated state with increased capacities for motility, protein synthesis, and proliferation. The present study determined, using Western analysis, double-label immunofluorescence and confocal microscopy, whether changes in phenotypic expression of rabbit aortic SMC in culture could be correlated with alterations in expression and distribution of structural proteins. "Contractile" state SMC (days 1 and 3 of primary culture) showed distinct sorting of proteins into subcellular domains, consistent with the theory that the SMC structural machinery is compartmentalised within the cell. Proteins specialised for contraction (,-SM actin, SM-MHC, and calponin) were highly expressed in these cells and concentrated in the upper central region of the cell. Vimentin was confined to the body of the cell, providing support for the contractile apparatus but not co-localising with it. In line with its role in cell attachment and motility, ,-NM actin was localised to the cell periphery and basal cortex. The dense body protein ,-actinin was concentrated at the cell periphery, possibly stabilising both contractile and motile apparatus. Vinculin-containing focal adhesions were well developed, indicating the cells' strong adhesion to substrate. In "synthetic" state SMC (passages 2,3 of culture), there was decreased expression of contractile and adhesion (vinculin) proteins with a concomitant increase in cytoskeletal proteins (,-non-muscle [NM] actin and vimentin). These quantitative changes in structural proteins were associated with dramatic changes in their distribution. The distinct compartmentalisation of structural proteins observed in "contractile" state SMC was no longer obvious, with proteins more evenly distributed throughout the cytoplasm to accommodate altered cell function. Thus, SMC phenotypic modulation involves not only quantitative changes in contractile and cytoskeletal proteins, but also reorganisation of these proteins. Since the cytoskeleton acts as a spatial regulator of intracellular signalling, reorganisation of the cytoskeleton may lead to realignment of signalling molecules, which, in turn, may mediate the changes in function associated with SMC phenotypic modulation. Cell Motil. Cytoskeleton 49:130,145, 2001. © 2001 Wiley-Liss, Inc. [source] Basic fibrobrast growth factor induces the secretion of vascular endothelial growth factor by human aortic smooth muscle cells but not by endothelial cellsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2003F. Belgore Abstract Background, Endothelial cell dysfunction and smooth muscle cell (SMC) proliferation are major events in atherogenesis. Both cells are a source of growth factors that mediate cellular proliferation and chemotaxis. Inappropriate production of, and/or response to, these growth factors (such as vascular endothelial growth factor, VEGF, and basic fibroblast growth factor (bFGF)) may contribute to atherogenesis and therefore to disease progression. Methods, Production of VEGF and its soluble receptor (sFlt-1) by human SMCs and human umbilical endothelial cells (HUVECs) after stimulation with bFGF were examined by ELISA of cell culture media and by Western blotting. Results, Smooth muscle cells produced significantly more VEGF than HUVECs (P < 0·05) after 24 h of culture with bFGF levels , 0·001 µg mL,1. bFGF induced dose-dependent production of VEGF by SMCs, where maximum production was present in 1 µg mL,1 of bFGF. Conversely, the SMCs produced less sFlt-1 than HUVECs (P < 0·05). However, bFGF induced dose-dependent phosphorylation of Flt1 and another VEGF receptor, KDR, in HUVECs but not SMCs. There was no VEGF or sFLT-1 after 6 h of culture in any dose of bFGF in either type of cell. Conclusions, Differences in the production of VEGF and sFlt-1 by SMCs and HUVECs are consistent with the role of these cells in angiogenesis. Induction of VEGF production and expression by bFGF in these cells indicates that this growth factor may participate in angiogenesis indirectly by the induction of VEGF. The production of sFlt-1 by both cell types is in agreement with the notion that sFlt-1 may be involved in the regulation of VEGF activity. Additionally, the ability of bFGF to induce dose-dependent phosphorylation of KDR in HUVECs highlights the important role of bFGF in VEGF-mediated angiogenic processes. [source] Smooth muscle cells in coronary atherosclerotic plaques: phenotypic variation and clinical consequencesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 11 2001Commentary No abstract is available for this article. [source] Effects of imatinib mesylate (Glivec®) as a c-kit tyrosine kinase inhibitor in the guinea-pig urinary bladderNEUROUROLOGY AND URODYNAMICS, Issue 3 2006Yasue Kubota Abstract Aims In the gastrointestinal tract, slow wave activity in smooth muscle is generated by the interstitial cells of Cajal (ICC). Detrusor smooth muscle strips of most species show spontaneous contractions which are triggered by action potential bursts, however, the pacemaker mechanisms for the detrusor are still unknown. Recently, ICC-like cells have been found in guinea-pig bladder, using antibodies to the c-kit receptor. We have investigated the effects of Glivec, a c-kit tyrosine kinase inhibitor, on spontaneous action potentials in guinea-pig detrusor and intravesical pressure of isolated guinea-pig bladders. Methods Changes in the membrane potential were measured in guinea-pig detrusor smooth muscle using conventional microelectrode techniques. Pressure changes in the bladder were recorded using whole organ bath techniques. Results Smooth muscle cells in detrusor muscle bundles exhibited spontaneous action potentials, and spontaneous pressure rises occurred in isolated bladders. Glivec (10 ,M) converted action potential bursts into continuous firing with no effects on the shape of individual action potentials. Glivec (>50 ,M) reduced the amplitude of spontaneous pressure rises in the whole bladder in a dose dependent manner and abolished spontaneous action potentials in detrusor smooth muscle cells. Conclusions The results suggest that ICC-like cells may be responsible for generating bursts of action potentials and contractions in detrusor smooth muscle. Drugs inhibiting the c-kit receptor may prove useful for treating the overactive bladder. Neurourol. Urodynam. © 2006 Wiley-Liss, Inc. [source] Alterations in connexin expression in the bladder of patients with urge symptomsBJU INTERNATIONAL, Issue 4 2005Jochen Neuhaus OBJECTIVE To compare the formation of gap junctions between detrusor smooth muscle cells in situ and the distribution of connexin (Cx)40, Cx43 and Cx45 expressions in bladder biopsies from a control group (with bladder tumour) and from patients with urge symptoms, as smooth muscle cells of the human detrusor muscle communicate via gap junctions and express several connexin subtypes, alterations of which may be involved in the causes of lower urinary tract symptoms. MATERIALS AND METHODS Connexin expression is prominent in myofibroblast-like cells, supposedly involved in afferent signalling pathways of the bladder. Their strategic position directly beneath the urothelium suggests they are a link between urothelial ATP signalling during bladder filling and afferent A,-fibre stimulation for co-ordination of bladder tonus and initialization of the micturition reflex. Modification of their coupling characteristics may have profound impact on bladder sensation. Bladder tissue probes of patients undergoing cystectomy or transurethral tumour resection for bladder cancer were used as controls. Tissue samples from patients with severe idiopathic urge symptoms were taken for exclusion diagnostics of interstitial cystitis (IC) and carcinoma in situ. The formation of functional syncytia between detrusor smooth muscle cells were examined in dye-coupling experiments by injecting with Lucifer Yellow. The morphology and structure of gap junctions were assessed by transmission electron microscopy and immunogold labelling of Cx43 and Cx45. The expression of connexin subtypes Cx40, Cx43 and Cx45 was compared by indirect immunofluorescence, and confocal laser scanning microscopy used for semiquantitative analysis. RESULTS There was dye coupling between smooth muscle cells of the detrusor in situ. Electron microscopy and immunogold labelling showed very small gap junctional plaques. These findings were confirmed by confocal immunofluorescence. Semiquantitative analyses showed significantly higher Cx43 expression in the detrusor muscle, and a tendency to higher Cx45 expression in the suburothelial layer associated with urge symptoms, whereas Cx40 expression was unaffected. CONCLUSIONS Smooth muscle cells of the human detrusor muscle are coupled by classical gap junctions, forming limited local functional syncytia. Both Cx43 and Cx45 are expressed at low levels in normal detrusor. Up-regulation of Cx43 in patients with urge incontinence supports the possibility of functional changes in the syncytial properties of detrusor smooth muscle cells in this condition. In addition, the observed increase of Cx45 in the myofibroblast cell layer supports the idea that alterations in sensory signalling are also involved. Comparison with previous reports implies that the pathophysiology of urgency is distinct from that of the unstable bladder and other forms of incontinence. [source] Regional variation in electrically-evoked contractions of rabbit isolated pulmonary arteryBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2002V Margaret Jackson Electrically-evoked contractions in different regions of the rabbit isolated pulmonary artery have been investigated using stimulation parameters generally assumed to stimulate nerves selectively. In extrapulmonary artery, trains of stimuli (10 Hz; pulse width 0.1 ms) evoked monophasic contractions. In contrast, a biphasic contraction was evoked in the intrapulmonary artery consisting of an initial fast component followed by a secondary very long-lasting component. The contraction in the extrapulmonary artery was prazosin-sensitive (1 ,M) whereas that in the intrapulmonary artery was prazosin-resistant. ,,,-Methylene ATP (1 ,M), atropine (1 ,M), losartan (1 ,M), BIBO3304 (1 nM) or nifedipine (1 ,M) had no effect on the biphasic contraction of the intrapulmonary artery. Bretylium (2 ,M) abolished the contraction of extrapulmonary artery but only partially inhibited the initial component in the intra region with no effect on the second component. Tetrodotoxin (0.3,1 ,M), abolished the contraction of extrapulmonary artery but only partially reduced the electrically-evoked contraction of intrapulmonary artery. Removal of the endothelium and application of sulphisoxazole (0.6,22 ,M) had no effect. Varying the resting tone on the arteries, or applying gadolinium, had no effect on contractions. Using confocal microscopy and calcium imaging, reproducible whole cell calcium transients were evoked in individual smooth muscle cells in intact preparations but only when direct muscle stimulation was used (pulse width of 5,10 ms). No detectable changes in calcium were elicited when brief pulse widths were used (0.1,2 ms). Together, these data suggest that noradrenaline is the neurotransmitter inducing contraction in extrapulmonary artery. Noradrenaline and sympathetic nerves appear to play a less important role in the intrapulmonary artery. The tetrodoxin-resistant component is not mediated by ATP, NPY, acetylcholine, angiotensins, ET-1, stretch-activation or Ca2+ influx through L-type Ca2+ channels. Smooth muscle cells do not appear to be damaged by the stimulation protocol. The mechanism underlying the long lasting contraction of intrapulmonary artery evoked by brief electrical stimuli remains to be elucidated. British Journal of Pharmacology (2002) 137, 488,496. doi:10.1038/sj.bjp.0704863 [source] Cell volume and rate of proliferation, but not protein expression pattern, distinguish pup/intimal smooth muscle cells from subcultured adult smooth muscle cellsCELL PROLIFERATION, Issue 5 2001E. McKilligin Smooth muscle cells from neonatal rats and from injured blood vessels grow with a characteristic cobblestone morphology that distinguishes them from adult smooth muscle cells. This has led to the proposition that there are two distinct types of smooth muscle cells with different proliferative capacity. Here we systematically compare the properties of subcultured adult smooth muscle cells in culture and clonal lines of cobblestone smooth muscle cells from both neonatal rats and injured vessels. The cobblestone smooth muscle cells have a significantly smaller average cell volume, estimated using two different flow cytometry measurements. However, the two types of smooth muscle cells have indistinguishable protein expression patterns when the levels of more than 20 different proteins (including cytoskeletal proteins, matrix proteins, cytokines, cytokine receptors, adhesion molecules and enzymes) are measured by quantitative immunofluorescence. Furthermore, in contrast to previous observations, we demonstrate that both types of smooth muscle cells secrete a powerful mitogenic activity. The higher cell density achieved by the cobblestone smooth muscle cells in culture was responsible for the earlier reports that this mitogenic activity was secreted only by cobblestone smooth muscle cells. We conclude that many of the differences seen between cobblestone smooth muscle cells and adult smooth muscle cells in vitro (proliferation rate, morphology, protein expression pattern, secretion of mitogenic activity) could be attributable to a stable difference in the median cell volume of the cultures. [source] Homocysteine is positively associated with cytokine IL-18 plasma levels in coronary artery bypass surgery patientsBIOFACTORS, Issue 2 2005Craig Steven Mclachlan Abstract Homocysteine, cytokines (IL-18, IL-6, IL-8) are involved in vascular inflammation and coronary artery disease. Homocysteine influences endothelial IL-6 and IL-8 cytokine expression and release, however, an association between homocysteine and IL-18 has not been previously investigated in endothelial/smooth muscle cells and or in coronary artery disease. We report in 9 coronary artery bypass surgery (CABG) patients a positive correlation r=0.86 between homocysteine and IL-18 plasma levels (p<0.05). Plasma IL-18 levels are significantly higher in those patients with elevated homocysteine compared to those with normal levels (p<0.02; 153 ± 19 pg/ml versus 116 ± 14 pg/ml respectively). Our in vitro cell culture studies suggest that the source of IL-18 in CABG patients with elevated homocysteine is not from vascular smooth muscle or endothelial cells. [source] G-CSF-mobilized peripheral blood mononuclear cells from diabetic patients augment neovascularization in ischemic limbs but with impaired capabilityJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 5 2006B. ZHOU Summary.,Background: Autologous transplantation of mobilized peripheral blood mononuclear cells (M-PBMNCs) is a novel approach to improve critical limb ischemia (CLI) in diabetes. However, endothelial progenitor cells (EPCs) from diabetes are dysfunctional and impaired in ischemia-induced neovascularization. Objective: This study aimed to confirm the compromised efficiency of diabetic M-PBMNCs in therapeutic neovascularization, and to determine the underlying mechanisms of this impairment. Methods: Diabetic M-PBMNCs from 17 diabetic patients or healthy controls, or phosphate-buffered saline (PBS) were injected into the ischemic limbs of streptozotocin-induced diabetic nude mice. The limb blood perfusion, ambulatory score, ischemia damage, capillary/fiber ratio, arteriole density, collateral vessel formation, and pericytes recruitment were evaluated between these three groups. Non-invasive real time image and histopathology were used to detect the in vivo role of transplanted M-PBMNCs. Proliferation and adhesion of EPCs were assayed. In vitro vascular network incorporation and matrigel plug assay were used to test the pro-neovascularization role of M-PBMNCs. Results: Transplantation of diabetic M-PBMNCs also improved neovascularization, but to a lesser extent from that observed with non-diabetic ones. This was associated with the impairment of diabetic M-PBMNCs capacity to differentiate into EPCs, to incorporate into vessel-like tubules in vitro, to participate in vascular-like structure formation in a subcutaneous matrigel plug, and to stimulate the recruitment of pericytes/smooth muscle cells. In addition, there was impairment in vasculogenesis, which was related to the reduced adhesion ability of EPCs from diabetic M-PBMNCs. Conclusions: Diabetes reduced the capacity of M-PBMNCs to augment neovascularization in ischemia. [source] ABSTRACTS: 1 Implication of soluble receptors of VEGF, sVEGFR-1 and sVEGFR-2, in angiogenesisAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 20082TH -6TH JUNE 2008 TOP SELECTED ABSTRACTS, 4TH EMBIC SUMMER SCHOOL, BARCELONA, SPAIN Introduction:, sVEGFR-1 and sVEGFR-2 are soluble forms of the membrane-bound receptors of VEGF. sVEGFR-1 is detected in plasma of pre-eclamptic women, during ischemia and in some cancer cases. sVEGFR-2, was recently detected in plasma of healthy people, in leukaemia and in systemic erythematosus lupus cases. sVEGFR-1 has anti-angiogenic properties in vitro and in vivo but sVEGFR-2 remains uncharacterized and its physiological or pathological role is still unknown. Material and Methods:, The aim of this study was to understand and to characterize the role of sVEGFR2 in angiogenesis and in endothelial function. Results:, In aortic ring assay, an ex vivo model of angiogenesis, sVEGFR1 and sVEGFR2 were able to abolish VEGF-induced angiogenesis. However, when used alone, they induced the formation of a "network", supposed to be vascular in visible microscopy. As they were able to abolish the effect of VEGF on endothelial function but showed no direct effect alone, we performed an immuno-staining of the "vascular network" induced by the soluble receptors. It showed that there were a few endothelial cells but mostly pericytes/smooth muscle cells (PC/SMC). Our first in vitro experiments on PC/SMC showed that sVEGFR-1 and sVEGFR-2 were able to promote the migration of PC/SMC, only in presence of endothelial cells. Conclusions:, Our results evidence that sVEGFR1 and sVEGFR2 inhibit VEGF-induced angiogenesis in a similar way. However, they have also a direct effect on PC/SMC, promoting their migration. Our results suggest that these soluble receptors could act, not only on endothelial cells themselves, but by a direct effect on PC/SMC too. These results contribute to identify factors by which it could be possible to regulate the balance between pro-angiogenic and anti-angiogenic factors, especially in the case of the anti-VEGF drugs used now as anti-cancer therapies in clinics, where a transient "normalization" of the vessels is observed. [source] Basic fibrobrast growth factor induces the secretion of vascular endothelial growth factor by human aortic smooth muscle cells but not by endothelial cellsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2003F. Belgore Abstract Background, Endothelial cell dysfunction and smooth muscle cell (SMC) proliferation are major events in atherogenesis. Both cells are a source of growth factors that mediate cellular proliferation and chemotaxis. Inappropriate production of, and/or response to, these growth factors (such as vascular endothelial growth factor, VEGF, and basic fibroblast growth factor (bFGF)) may contribute to atherogenesis and therefore to disease progression. Methods, Production of VEGF and its soluble receptor (sFlt-1) by human SMCs and human umbilical endothelial cells (HUVECs) after stimulation with bFGF were examined by ELISA of cell culture media and by Western blotting. Results, Smooth muscle cells produced significantly more VEGF than HUVECs (P < 0·05) after 24 h of culture with bFGF levels , 0·001 µg mL,1. bFGF induced dose-dependent production of VEGF by SMCs, where maximum production was present in 1 µg mL,1 of bFGF. Conversely, the SMCs produced less sFlt-1 than HUVECs (P < 0·05). However, bFGF induced dose-dependent phosphorylation of Flt1 and another VEGF receptor, KDR, in HUVECs but not SMCs. There was no VEGF or sFLT-1 after 6 h of culture in any dose of bFGF in either type of cell. Conclusions, Differences in the production of VEGF and sFlt-1 by SMCs and HUVECs are consistent with the role of these cells in angiogenesis. Induction of VEGF production and expression by bFGF in these cells indicates that this growth factor may participate in angiogenesis indirectly by the induction of VEGF. The production of sFlt-1 by both cell types is in agreement with the notion that sFlt-1 may be involved in the regulation of VEGF activity. Additionally, the ability of bFGF to induce dose-dependent phosphorylation of KDR in HUVECs highlights the important role of bFGF in VEGF-mediated angiogenic processes. [source] Evidence for an endothelium-derived hyperpolarizing factor in the superior mesenteric artery from rats with cirrhosisHEPATOLOGY, Issue 5 2000Eric Barriere In cirrhosis, in splanchnic arteries, endothelium-dependent relaxation may persist even if overactive nitric oxide synthase (NOS) and cyclooxygenase (COX) are inhibited. In normal arteries, a significant endothelium-dependent relaxation to acetylcholine persists after NOS/COX inhibition. This relaxation is caused by smooth muscle cell (SMC) membrane hyperpolarization, which is sensitive to a combination of the potassium channel blockers apamin and charybdotoxin, and is mediated by an endothelium-derived hyperpolarizing factor (EDHF). The aim of this study was to detect EDHF and evaluate its pathophysiologic role in isolated superior mesenteric arteries from cirrhotic rats. Arterial rings were obtained and exposed to Nw -nitro-L-arginine (L-NNA, a NOS inhibitor) and indomethacin (a COX inhibitor). Acetylcholine-induced membrane potential responses and concentration-response curves to the relaxant of acetylcholine were obtained with and without apamin plus charybdotoxin. Acetylcholine-induced responses were measured in certain rings from endothelium-denuded arteries. Contractions caused by the ,1 -adrenoceptor agonist phenylephrine were obtained in cirrhotic and normal rings with and without apamin and charybdotoxin. Significant acetylcholine-induced, endothelium-dependent, apamin- and charybdotoxin-sensitive, SMC membrane hyperpolarization and relaxation were found. An apamin- and charybdotoxin-sensitive hyporesponsiveness to the contractile action of phenylephrine was found in cirrhotic rings. In conclusion, in cirrhotic rats, in the superior mesenteric artery exposed to NOS/COX-inhibitors, an EDHF exists that may replace NOS/COX products to induce endothelium-dependent arterial relaxation. [source] Bladder smooth muscle cell phenotypic changes and implication of expression of contractile proteins (especially caldesmon) in rats after partial outlet obstructionINTERNATIONAL JOURNAL OF UROLOGY, Issue 6 2003SEIJI MATSUMOTO Abstract Background: The purpose of the present study was to investigate morphological changes in bladder smooth muscle of rats with partial outlet obstruction. We investigated smooth muscle cell phenotypic changes and implication of synthetic phenotype in contractility decrease and bladder compliance after bladder outlet obstruction. Methods: Partial bladder outlet obstruction was introduced in female rats. Bladder were removed at 1, 3, 6, 10 and 20 weeks after the obstruction. Temporal pattern of changes in bladder mass, light microscopic pathogenesis and phenotypic expression of the bladder smooth muscle cells in the electron micrographs were investigated. Expression of contractile protein was also investigated by the immunoblotting method. Results: Marked increase in bladder mass with marked thickening of smooth muscle layer was observed at 1 week after obstruction. The ratio of myocytes exhibiting contractile and synthetic phenotypes was almost constant until 6 weeks after the obstruction, but thereafter, synthetic phenotypes gradually increased and the ratio (synthetic/contractile phenotype) was 1.5-fold at 20 weeks after the obstruction. Caldesmon was most markedly expressed after the obstruction among contractile proteins examined by the immunoblotting method. Conclusion: Phenotypic changes were confirmed in bladder smooth muscle, and the decrease of the ratio of contractile phenotype was observed after long-term obstruction of the bladder outlet. Among the contractile proteins in the bladder smooth muscle cell, caldesmon was considered a reliable marker for predicting the pathogenetic conditions of the bladder. [source] High-phosphate-induced calcification is related to SM22, promoter methylation in vascular smooth muscle cellsJOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2010Addy Montes de Oca Abstract Hyperphosphatemia is closely related to vascular calcification in patients with chronic kidney disease. Vascular smooth muscle cells (VSMCs) exposed to high phosphate concentrations in vitro undergo phenotypic transition to osteoblast-like cells. Mechanisms underlying this transdifferentiation are not clear. In this study we used two in vitro models, human aortic smooth muscle cells and rat aortic rings, to investigate the phenotypic transition of VSMCs induced by high phosphate. We found that high phosphate concentration (3.3,mmol/L) in the medium was associated with increased DNA methyltransferase activity and methylation of the promoter region of SM22,. This was accompanied by loss of the smooth muscle cell,specific protein SM22,, gain of the osteoblast transcription factor Cbfa1, and increased alkaline phosphatase activity with the subsequent in vitro calcification. The addition of a demethylating agent (procaine) to the high-phosphate medium reduced DNA methyltransferase activity and prevented methylation of the SM22, promoter, which was accompanied by an increase in SM22, expression and less calcification. Additionally, downregulation of SM22,, either by siRNA or by a methyl group donor (S -adenosyl methionine), resulted in overexpression of Cbfa1. In conclusion, we demonstrate that methylation of SM22, promoter is an important event in vascular smooth muscle cell calcification and that high phosphate induces this epigenetic modification. These findings uncover a new insight into mechanisms by which high phosphate concentration promotes vascular calcification. © 2010 American Society for Bone and Mineral Research [source] Differential Effects of Vitamin D Analogs on Vascular Calcification,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2007Anna Cardús Abstract We tested the effects of calcitriol and its analog paricalcitol on VSMC calcification in vitro and in vivo. For that reason, cells and animals with five-sixths nephrectomy were treated with both compounds. Calcitriol, but not paricalcitol, increased VSMC calcification in vitro and in vivo independently of calcium and phosphate levels. This increase in calcification was parallel to an increase in the RANKL/OPG ratio. Introduction: Vascular calcification is a common finding in patients with endstage renal disease. Furthermore, those patients often present secondary hyperparathyroidism, partly because of a decrease of calcitriol synthesis on the kidney. Thus, one of the main therapeutic options is to treat those patients with calcitriol or analogs. However, this treatment presents unwanted side effects, such as increases in vascular calcification. Materials and Methods: We tested the effect on vascular smooth muscle cell (VSMC) calcification of calcitriol and one of its analogs, paricalcitol, in vitro and in vivo in animals with endstage renal disease. Results: Calcitriol increased calcification of VSMCs cultured in calcification media. This effect was not present when cells were incubated with paricalcitol. Furthermore, only cells incubated with calcitriol showed an increased RANKL/ osteoprotegerin (OPG) expression. Animals with renal failure treated with hypercalcemic doses of calcitriol and paricalcitol showed an increase in systolic blood pressure. However, diastolic blood pressure only raised significantly in those animals treated with paricalcitol. This effect led to a significant increase in pulse pressure in animals treated with calcitriol. The increase in pulse pressure was likely caused by the extensive calcification observed in arteries of animals treated with calcitriol. This increase in calcification was not seen in arteries of animals treated with paricalcitol, despite having similar levels of serum calcium and phosphorus as animals treated with calcitriol. Furthermore, the decreases in serum PTH levels were similar in both treatments. Conclusions: We conclude that paricalcitol has a different effect than calcitriol in VSMC calcification and that this could explain part of the differences observed in the clinical settings. [source] Close relation of arterial ICC-like cells to the contractile phenotype of vascular smooth muscle cellJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 4 2007Vladimír Pucovský Abstract This work aimed to establish the lineage of cells similar to the interstitial cells of Cajal (ICC), the arterial ICC-like (AIL) cells, which have recently been described in resistance arteries, and to study their location in the artery wall. Segments of guinea-pig mesenteric arteries and single AIL cells freshly isolated from them were used. Confocal imaging of immunostained cells or segments and electron microscopy of artery segments were used to test for the presence and cellular localization of selected markers, and to localize AIL cells in intact artery segments. AIL cells were negative for PGP9.5, a neural marker, and for von Willebrand factor (vWF), an endothelial cell marker. They were positive for smooth muscle ,-actin and smooth muscle myosin heavy chain (SM-MHC), but expressed only a small amount of smoothelin, a marker of contractile smooth muscle cells (SMC), and of myosin light chain kinase (MLCK), a critical enzyme in the regulation of smooth muscle contraction. Cell isolation in the presence of latrunculin B, an actin polymerization inhibitor, did not cause the disappearance of AIL cells from cell suspension. The fluorescence of basal lamina protein collagen IV was comparable between the AIL cells and the vascular SMCs and the fluorescence of laminin was higher in AIL cells compared to vascular SMCs. Moreover, cells with thin processes were found in the tunica media of small resistance arteries using transmis-sion electron microscopy. The results suggest that AIL cells are immature or phenotypically modulated vascular SMCs constitutively present in resistance arteries. [source] | |||||||||||||||||||||||||||||||||||||