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Endothelial Cell Proliferation (endothelial + cell_proliferation)
Selected AbstractsChemInform Abstract: Synthesis and Biological Evaluation of Novel Bisindolylmaleimides that Inhibit Vascular Endothelial Cell Proliferation.CHEMINFORM, Issue 4 2002Miguel F. Brana Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Noninvasive Imaging of Angiogenesis Inhibition Following Nitric Oxide Synthase Blockade in the Ischemic Rat Heart in VivoMICROCIRCULATION, Issue 4 2005CHRISTIANE WALLER MD ABSTRACT Objective: Nitric oxide synthase inhibition has anti-angiogenic properties. Magnetic resonance (MR) imaging was used to image the functional significance of these microvascular changes in a rat model of chronic ischemic myocardium in vivo. Methods: The authors quantitatively determined myocardial perfusion and regional blood volume, left ventricular geometry, and function using MR imaging. Animals received either L-NAME + hydralazine or no treatment and were investigated 1 and 2 weeks after induction of coronary artery stenosis or sham operation at rest and during vasodilatation. Double-labeling immunohistochemistry was used to visualize angiogenesis and to compare with data obtained by MR imaging. Results: Left ventricular mass and end-diastolic volumes were comparable in both groups 2 weeks after treatment. However, basal and maximum perfusion in animals with L -NAME + hydralazine treatment were reduced compared to animals not treated (p < .05). Basal regional blood volume remained constant in all groups, whereas maximum regional blood volume was reduced by L -NAME + hydralazine (p < .05). Endothelial cell proliferation, a direct marker for angiogenesis, was reduced by L -NAME + hydralazine (p < .01). Conclusions: MR imaging allows noninvasive quantification of functional microcirculation and angiogenesis in the rat heart in vivo. Nitric oxide synthase blockade results in changes in functional microcirculation and in an inhibition of angiogenesis in both ischemic and nonischemic myocardial tissue. [source] Signalling pathways involved in retinal endothelial cell proliferation induced by advanced glycation end products: inhibitory effect of gliclazideDIABETES OBESITY & METABOLISM, Issue 2 2004J.-C. Mamputu Aim:, We have previously demonstrated that advanced glycation end products (AGEs) stimulate bovine retinal endothelial cell (BREC) proliferation through induction of vascular endothelial growth factor (VEGF) production by these cells. We have also shown that gliclazide, a sulfonylurea which decreases oxidative stress, inhibits this effect. The aim of the present study was to characterize the signalling pathways involved in AGE-induced BREC proliferation and VEGF production and mediating the inhibitory effect of gliclazide on these biological events. Methods:, BRECs were treated or not treated with AGEs in the presence or absence of gliclazide, antioxidants, protein kinase C (PKC), mitogen-activated protein kinase (MAPK) or nuclear factor-,B (NF-,B) inhibitors. BREC proliferation was assessed by measuring [3H]-thymidine incorporation into DNA. Activation of PKC, MAPK and NF-,B signal transduction pathways and determination of VEGF expression were assessed by Western blot analysis using specific antibodies. MAPK activity was also determined by an in vitro kinase assay. Results:, Treatment of BRECs with AGEs significantly increased cell proliferation and VEGF expression. AGEs induced PKC-, translocation, extracellular signal-regulated protein kinase 1/2 and NF-,B activation in these cells. Pharmacological inhibition of these signalling pathways abolished AGE effects on cell proliferation and VEGF expression. Exposure of BRECs to gliclazide or antioxidants such as vitamin E or N -acetyl- l -cysteine resulted in a significant decrease in AGE-induced activation of PKC-, MAPK- and NF-,B-signalling pathways. Conclusions:, Our results demonstrate the involvement of PKC, MAPK and NF-,B in AGE-induced BREC proliferation and VEGF expression. Gliclazide inhibits BREC proliferation by interfering with these intracellular signal transduction pathways. [source] Parathyroid hormone stimulates the endothelial expression of vascular endothelial growth factorEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 11 2008G. Rashid ABSTRACT Background, We showed previously that parathyroid hormone (PTH) may stimulate the endothelial expression of pro-atherosclerotic and pro-inflammatory markers. Considering the impact of PTH on vasculature, we decided to evaluate its effect on mRNA and intra-cellular protein expressions of endothelial vascular endothelial growth factor (VEGF) taking into account that VEGF may play a role in the pathogenesis of endothelial dysfunctions. Materials and methods, Human umbilical vein cords endothelial cells (HUVEC) were stimulated for 24 h with 10,12,10,10 mol L,1 PTH. The VEGF-165 mRNA expression (critical in stimulating endothelial cell proliferation) was evaluated by RT/PCR and the intra-cellular VEGF protein expression by flow cytometry. The pathways by which PTH may have an effect on VEGF expression were also evaluated. Results, PTH (10,10 mol L,1) significantly increased VEGF-165 mRNA expression (P < 0·05). The addition of 50 nmol L,1 protein kinase C (PKC) and 10 µmol L,1 protein kinase A (PKA) inhibitors significantly reduced the VEGF-165 mRNA expression (P = 0·01). We also examined whether nitric oxide (NO) may be involved in the PTH-induced stimulation of VEGF-165 expression. Pre-treatment of the cells with 200 µmol L-nitro arginine methyl ester (L-NAME, NO synthase inhibitor) was found to inhibit VEGF-165 mRNA expression (P = 0·006). VEGF protein could not be detected in the medium of HUVEC but it was present in the cell cytoplasm. PTH had no significant effect on cytoplasmatic VEGF protein expression. Conclusion, The stimulatory effect of PTH on endothelial VEGF-165 mRNA expression is partly through PKC and PKA pathways and is also NO dependent. [source] In the hypoxic central nervous system, endothelial cell proliferation is followed by astrocyte activation, proliferation, and increased expression of the ,6,4 integrin and dystroglycanGLIA, Issue 10 2010Longxuan Li Abstract Cerebral hypoxia induces a profound angiogenic response in the central nervous system (CNS). Using a mouse model of chronic cerebral hypoxia, we previously demonstrated that angiogenic vessels in the hypoxic CNS show marked upregulation of the extracellular matrix (ECM) protein fibronectin, along with increased expression of its major receptor, ,5,1 integrin on brain endothelial cells (BEC). As cerebral hypoxia also leads to glial activation, the aim of the current study was to define the temporal relationship between BEC responses and glial cell activation in this model of cerebral hypoxia. This revealed that BEC fibronectin/,5,1 integrin expression and proliferation both reached maximal level after 4-day hypoxia. Interestingly, up to 4-day hypoxia, all dividing cells were BEC, but at later time-points proliferating astrocytes were also observed. GFAP staining revealed that hypoxia induced marked astrocyte activation that reached maximal level between 7- and 14-day hypoxia. As newly formed cerebral capillaries require ensheathment by astrocyte end-feet to acquire mature brain endothelium characteristics, we next examined how expression of astrocyte end-feet adhesion molecules is regulated by hypoxia. This showed that the astrocyte adhesion receptors ,6,4 integrin and dystroglycan were both markedly upregulated, with a time-course that closely resembled astrocyte activation. Taken together, this evidence shows that cerebral hypoxia promotes first an endothelial response, in which fibronectin promotes BEC proliferation. This is then followed by an astrocyte response, involving astrocyte activation, proliferation, and reorganization of astrocyte end-feet, which correlates with increased expression of astrocyte end-feet adhesion molecules. © 2010 Wiley-Liss, Inc. [source] Patients with bisphosphonates-associated osteonecrosis of the jaw have reduced circulating endothelial cellsHEMATOLOGICAL ONCOLOGY, Issue 4 2007A Allegra Abstract Osteonecrosis of the jaws (ONJ) associated with the use of bisphosphonates is a newly described entity. To elucidate the mechanism leading to ONJ and to test the hypothesis that in patients with ONJ the bisphosphonates may interfere with endothelial cell proliferation, using flow cytometric analysis we evaluated the number of circulating endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) in eight patients with bisphosphonate treatment and osteonecrosis, eight multiple myeloma (MM) patients with bisphosphonates treatment without ONJ and five normal subjects. MM patients showed an increase of CD34+ cells with respect the control subjects and ONJ subjects. EPCs and CECs were higher in MM patients compared to controls and ONJ patients. ONJ patients showed a decrease of EPCs compared to control subjects while CECs were similar to the controls group. Our results seem to show the possibility that bisphosphonates could have a antiangiogenic effect and a suppressive effect on CECs of patients with ONJ. Copyright © 2007 John Wiley & Sons, Ltd. [source] Increased plasma MMP9 in integrin ,1-null mice enhances lung metastasis of colon carcinoma cellsINTERNATIONAL JOURNAL OF CANCER, Issue 1 2005Xiwu Chen Abstract Inhibitors of matrix metalloproteinases (MMPs) were developed as anticancer agents based on the observation that MMPs facilitate local tumor spread and metastasis by promoting matrix degradation and cell migration. Unfortunately, these inhibitors were unsuccessful in the clinical treatment of several cancers, including lung cancer. A possible reason contributing to their failure is that MMP activity is critical for the generation of inhibitors of tumor angiogenesis, including angiostatin. Thus, MMPs might play opposing roles in tumor vascularization and invasion. To determine which effect of elevated MMP levels dominates in the progression of metastatic cancer, experimental lung metastasis assays were performed in integrin ,1-null mice, a genetic model for increased plasma levels of MMP9 and MMP9-generated angiostatin (Pozzi et al., Proc. Natl. Acad. Sci. USA 2000;97:2202,7). We show that while the number of lung colonies in integrin ,1-null mice was significantly increased compared to their wild-type counterparts, tumor volume was markedly reduced. In vivo treatment with the MMP inhibitor doxycycline resulted in a significant decrease in the number of lung colonies in both genotypes, but the tumors that formed were bigger and more vascularized. Increased tumor vascularization paralleled decreased plasma levels of MMP9 and consequent decreased angiostatin synthesis. These results demonstrate that while inhibition of MMPs prevents and/or reduces tumor invasion and lung metastasis, it has the paradoxical effect of increasing the size and vascularization of metastatic tumors due to decreased generation of inhibitors of endothelial cell proliferation. The continued growth of these large well-vascularized tumors may explain the poor efficacy of MMP inhibitors in lung cancer clinical trials. © 2005 Wiley-Liss, Inc. [source] A critical analysis of current in vitro and in vivo angiogenesis assaysINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 3 2009Carolyn A. Staton Summary The study of angiogenesis has grown exponentially over the past 40 years with the recognition that angiogenesis is essential for numerous pathologies and, more recently, with the advent of successful drugs to inhibit angiogenesis in tumours. The main problem with angiogenesis research remains the choice of appropriate assays to evaluate the efficacy of potential new drugs and to identify potential targets within the angiogenic process. This selection is made more complex by the recognition that heterogeneity occurs, not only within the endothelial cells themselves, but also within the specific microenvironment to be studied. Thus, it is essential to choose the assay conditions and cell types that most closely resemble the angiogenic disease being studied. This is especially important when aiming to translate data from in vitro to in vivo and from preclinical to the clinic. Here we critically review and highlight recent advances in the principle assays in common use including those for endothelial cell proliferation, migration, differentiation and co-culture with fibroblasts and mural cells in vitro, vessel outgrowth from organ cultures and in vivo assays such as chick chorioallantoic membrane (CAM), zebrafish, sponge implantation, corneal, dorsal air sac, chamber and tumour angiogenesis models. Finally, we briefly discuss the direction likely to be taken in future studies, which include the use of increasingly sophisticated imaging analysis systems for data acquisition. [source] VEGF in biological controlJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2007Ellen C. Breen Abstract Vascular endothelial growth factor A (VEGF-A) belongs to a family of heparin binding growth factors that include VEGF-B, VEGF-C, VEGF-D, and placental-like growth factor (PLGF). First discovered for its ability to regulate vascular endothelial cell permeability, VEGF is a well-known angiogenic factor that is important for vascular development and maintenance in all mammalian organs. The development of molecular tools and pharmacological agents to selectively inhibit VEGF function and block angiogenesis and/or vascular permeability has led to great promise in the treatment of various cancers, macular degeneration, and wound healing. However, VEGF is also important in animals for the regulation of angiogenesis, stem cell and monocyte/macrophage recruitment, maintenance of kidney and lung barrier functions and neuroprotection. In addition to its role in regulating endothelial cell proliferation, migration, and cell survival, VEGF receptors are also located on many non-endothelial cells and act through autrocrine pathways to regulate cell survival and function. The following review will discuss the role of VEGF in physiological angiogenesis as well as its role in non-angiogenic processes that take place in adult organs. J. Cell. Biochem. 102: 1358,1367, 2007. © 2007 Wiley-Liss, Inc. [source] Cloning and characterization of angiocidin, a tumor cell binding protein for thrombospondin-1JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2004Jing Zhou Abstract Thrombospondin-1 (TSP-1) is a matrix protein that has been implicated in mechanisms of tumor progression. Our laboratory previously showed that the CSVTCG (cys-ser-val-thr-cys-gly) sequence of TSP-1 functioned as a tumor cell adhesion domain and CSVTCG peptides as well as an anti-peptide antibody possessed anti-metastatic activity in a murine model of lung metastasis. In a subsequent study, a putative TSP-1 binding protein from lung carcinoma was isolated by CSVTCG-peptide affinity chromatography. In this study, we present the full-length cDNA of this binding protein isolated from a prostate cancer cell (PC3-NI) cDNA library. The purified recombinant protein, termed angiocidin, is a potent inhibitor of tumor growth of Lewis Lung carcinoma in vivo and tumor invasion and angiogenesis in vitro. In addition, the recombinant protein inhibits tumor and endothelial cell proliferation and induces apoptosis. The activity of angiocidin both in vivo and in vitro is partially dependent on its TSP-1 binding activity, since an angiocidin deletion mutant missing a high affinity-binding site for TSP-1 failed to inhibit tumor growth in vivo and was less active in its anti-tumor and anti-angiogenic activities in vitro. These results suggest that the anti-tumor activity of TSP-1 reported in many studies may be mediated in part by binding proteins such as angiocidin. Such proteins may function as tumor-suppressor proteins, which limit the growth of tumors by inhibiting angiogenesis and cell matrix interaction. © 2004 Wiley-Liss, Inc. [source] Epidermal growth factor released from platelet-rich plasma promotes endothelial cell proliferation in vitroJOURNAL OF PERIODONTAL RESEARCH, Issue 1 2010M.-P. Bertrand-Duchesne Bertrand-Duchesne M-P, Grenier D, Gagnon G. Epidermal growth factor released from platelet-rich plasmapromotes endothelial cell proliferation in vitro. J Periodont Res 2009; doi: 10.1111/j.1600-0765.2009.01205.x. © 2009 The Authors. Journal compilation © 2009 Blackwell Munksgaard Background and Objective:, The therapeutic benefits of platelet-rich plasma (PRP) for the promotion of healing and regeneration of periodontal tissues are thought to result from enrichment in growth factors released from platelets. The aim of this study was to evaluate the effects of specific growth factors released from PRP on endothelial cell proliferation. Material and Methods:, The levels of vascular endothelial growth factor (VEGF), platelet-derived growth factor BB (PDGF-BB), basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) in supernatants of calcium- and thrombin-activated PRP samples from five donors were quantified by enzyme-linked immunosorbent assay. Supernatants were treated with neutralizing antibodies specific to each growth factor, and the effects of these treatments on human umbilical vein endothelial cell (HUVEC) proliferation in vitro were determined. The effect of removing EGF from PRP supernatants with antibody-coated beads on HUVEC proliferation was also tested. Results:, Average concentrations of VEGF, PDGF-BB, bFGF and EGF in PRP supernatants were 189, 27,190, 39.5 and 513 pg/mL, respectively. The addition of EGF neutralizing antibodies to the PRP supernatants significantly reduced HUVEC proliferation (up to 40%), while such an inhibition was not observed following neutralization of the other growth factors. Removal of EGF from PRP supernatants by treatment with antibody-coated beads also resulted in a significant decrease in HUVEC proliferation. Recombinant EGF increased HUVEC proliferation in vitro in a dose-dependent manner. Conclusion:, This study showed that PRP supernatants are highly mitogenic for endothelial cells and provided evidence that this effect may be due, at least in part, to the presence of EGF. In vivo experiments are needed to confirm the roles of specific growth factors released from PRP in the healing of oral surgical and/or periodontal wounds. [source] Antiangiogenic drugs: Current knowledge and new approaches to cancer therapyJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2008Jose L. Mauriz Abstract Angiogenesis,process of new blood-vessel growth from existing vasculature,is an integral part of both normal developmental processes and numerous pathologies such as cancer, ischemic diseases and chronic inflammation. Angiogenesis plays a crucial role facilitating tumour growth and the metastatic process, and it is the result of a dynamic balance between proangiogenic and antiangiogenic factors. The potential to block tumour growth and metastases by angiogenesis inhibition represents an intriguing approach to the cancer treatment. Angiogenesis continues to be a topic of major scientific interest; and there are currently more antiangiogenic drugs in cancer clinical trials than those that fit into any other mechanistic category. Based on preclinical studies, researchers believe that targeting the blood vessels which support tumour growth could help treatment of a broad range of cancers. Angiogenic factors or their receptors, endothelial cell proliferation, matrix metalloproteinases or endothelial cell adhesion, are the main targets of an increasing number of clinical trials approved to test the tolerance and therapeutic efficacy of antiangiogenic agents. Unfortunately, contrary to initial expectations, it has been described that antiangiogenic treatment can cause different toxicities in cancer patients. The purpose of this article is to provide an overview of current attempts to inhibit tumour angiogenesis for cancer therapy. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:4129,4154, 2008 [source] Endostatin Concentrations in Healthy Dogs and Dogs with Selected NeoplasmsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 5 2002John H. Rossmeisl Jr Endostatin prevents angiogenesis and tumor growth by inhibiting endothelial cell proliferation and migration. The purpose of this study was to determine serum endostatin concentrations in 53 healthy dogs and in 38 dogs with confirmed malignant neoplasms. Endostatin concentration was determined with a competitive enzymatic immunoassay (EIA) with rabbit polyclonal antibody generated against a recombinant canine endostatin protein. Both the presence of cancer and increasing age were associated with increased serum concentration of endostatin. Endostatin concentration in healthy dogs was 87.7 ± 3.5 ng/mL. Upper and lower limits of the reference range for serum endostatin concentration in healthy dogs were 60 and 113 ng/mL. Dogs with lymphoma (LSA) and hemangiosarcoma (HSA) had endostatin concentrations of 107 ± 9.3 ng/mL. In conclusion, this study demonstrates that endostatin can be quantified in dogs and that endostatin concentrations are high in dogs with HSA and LSA. [source] The role of eosinophil major basic protein in angiogenesisALLERGY, Issue 3 2009I. Puxeddu Background:, Eosinophil-derived major basic protein (MBP) plays an active role in allergic inflammation and tissue remodelling. However, its role in angiogenesis has not been established as yet. Therefore our objective was to investigate whether MBP exhibits any direct pro-angiogenic effects. Methods:, Rat aortic endothelial cells and human umbilical vascular endothelial cells were cultured with different concentrations of MBP and their viability (Trypan blue exclusion test), proliferation (thymidine incorporation) and capillary-like structure formation (matrigel assay) were investigated in vitro. The angiogenic activity of MBP was then tested in vivo using the chick chorio allantoic membrane (CAM) assay. Results:, Subcytotoxic concentrations of MBP induce endothelial cell proliferation and enhance the pro-mitogenic effect of vascular endothelial growth factor (VEGF), but do not affect their VEGF release. MBP promotes capillarogenesis by endothelial cells seeded on matrigel and sprouting formation in the CAM assay. Furthermore, we have shown that the pro-angiogenic effect of MBP is not due to its cationic charge since stimulation of the CAMs with the synthetic polycation, poly- l -arginine does not induce any angiogenic effects. Conclusions:, These data demonstrate that MBP has pro-angiogenic effects in vitro and in vivo, providing a novel mechanism whereby MBP can participate in tissue inflammation and remodelling in atopic diseases. [source] Phytochemicals in olive-leaf extracts and their antiproliferative activity against cancer and endothelial cellsMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 5 2009Vlassios Goulas Abstract Olive oil compounds is a dynamic research area because Mediterranean diet has been shown to protect against cardiovascular disease and cancer. Olive leaves, an easily available natural material of low cost, share possibly a similar wealth of health benefiting bioactive phytochemicals. In this work, we investigated the antioxidant potency and antiproliferative activity against cancer and endothelial cells of water and methanol olive leaves extracts and analyzed their content in phytochemicals using LC-MS and LC-UV-SPE-NMR hyphenated techniques. Olive-leaf crude extracts were found to inhibit cell proliferation of human breast adenocarcinoma (MCF-7), human urinary bladder carcinoma (T-24) and bovine brain capillary endothelial (BBCE). The dominant compound of the extracts was oleuropein; phenols and flavonoids were also identified. These phytochemicals demonstrated strong antioxidant potency and inhibited cancer and endothelial cell proliferation at low micromolar concentrations, which is significant considering their high abundance in fruits and vegetables. The antiproliferative activity of crude extracts and phytochemicals against the cell lines used in this study is demonstrated for the first time. [source] The modulation of endothelial cell gene expression by green tea polyphenol-EGCGMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 10 2008Liping Liu Abstract Human and animal studies have shown that green tea consumption is associated with a reduced risk of some cancers. This has been attributed to its polyphenol components, in particular (,)-epigallocatechin gallate (EGCG). In addition to be a cancer chemopreventive agent, EGCG inhibits angiogenesis, thus reducing tumor growth and metastasis. We tested EGCG modulation on the gene expression profile of endothelial cells stimulated by VEGF using Affymetrix microarrays. A total of 421 genes were up-regulated and 72 genes were down-regulated at the false discovery rate of 5% by VEGF, EGCG, and EGCG pretreatment followed by VEGF stimulation. The changes in the expression of several pivotal genes were validated by real-time PCR. Furthermore, we have identified two signaling pathways (Wnt and Id) involved in cell proliferation were inhibited by EGCG treatment, suggesting the negative regulation of EGCG on cell proliferation. Our results also indicate that the antiangiogenesis effect of EGCG is partially mediated through its broad inhibition on endothelial cell proliferation. Our data further support earlier observations that the anticancer effect of EGCG is mediated through changes in the expression of genes that are associated with cell proliferation. [source] Promigratory Activity of Oxytocin on Umbilical Cord Blood-Derived Mesenchymal Stem CellsARTIFICIAL ORGANS, Issue 6 2010Yong Sook Kim Abstract Recent studies show that oxytocin has various effects on cellular behaviors. Oxytocin is reported to stimulate cardiomyogenesis of embryonic stem cells and endothelial cell proliferation. Mesenchymal stem cells (MSCs) are widely used for cardiac repair, and we elucidated the effect of oxytocin on umbilical cord derived-MSCs (UCB-MSCs). UCB-MSCs were pretreated with oxytocin (100 nM) and washed with saline prior to experiments. To evaluate their angiogenic potential and migration activity, tube formation assay and Boyden chamber assay were performed. For in vivo study, ischemia-reperfusion was induced in rats, and UCB-MSCs with or without oxytocin pretreatment were injected into the infarcted myocardium to evaluate the engraftment of injected cells. Histological and hemodynamic studies were performed. Oxytocin-treated UCB-MSCs showed a decrease in tube formation but a drastic increase in transwell migration activity. The transcription level of matrix metalloproteinase (MMP)-2 was increased in oxytocin-treated UCB-MSCs. Knock-down of MMP-2 by use of siRNA restored the tube formation, while reducing transmigration activity. In rats injected with oxytocin-treated UCB-MSCs, cardiac fibrosis and CD68 infiltration in the peri-infarct zone were reduced, whereas cell engraftment and connexin43 expression were greater than in rats injected with untreated UCB-MSCs. By contrast, angiogenesis did not differ significantly between the two groups. Cardiac contractility was higher in the group injected with oxytocin-treated UCB-MSCs than in the group injected with phosphate-buffered saline alone. Collectively, oxytocin is an effective priming reagent for stem cells for application to damaged heart tissue. [source] Purinergic regulation of vascular tone and remodellingAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 3 2009G. Burnstock Summary 1 Purinergic signalling is involved both in short-term control of vascular tone and in longer-term control of cell proliferation, migration and death involved in vascular remodelling. 2 There is dual control of vascular tone by adenosine 5,-triphosphate (ATP) released from perivascular nerves and by ATP released from endothelial cells in response to changes in blood flow (shear stress) and hypoxia. 3 Both ATP and its breakdown product, adenosine, regulate smooth muscle and endothelial cell proliferation. 4 These regulatory mechanisms are important in pathological conditions, including hypertension, atherosclerosis, restenosis, diabetes and vascular pain. [source] The in vitro response of human retinal endothelial cells to cytokines and other chemically active agents is altered by coculture with vitreous-derived hyalocytesACTA OPHTHALMOLOGICA, Issue 3 2010Naoki Tojo Abstract. Background:, Ocular angiogenesis is regulated by polypeptides including cytokines, which are known to affect vascular endothelial cells. We have reported that hyalocytes interact with vascular endothelial cells, and some cytokines affect these interactions. Aims:, To determine the effect of various chemically active agents on the viability of endothelial cells alone and cocultured with hyalocytes. Methods:, The viability of human retinal endothelial cells (HRECs) was determined after exposure to IL-1,, IL-1,, IL-6, TNF, and VEGF using the MTT assay. These results were compared to the viability when the HRECs were cocultured with porcine hyalocytes that had been exposed to different types of cytokines. The effects of bevacizumab, fenofibrate and dexamethasone on the viability of HRECs in coculture with hyalocytes were also assessed. Results:, Ten micrograms/millilitre of bevacizumab decreased the percentage of living HRECs stimulated by VEGF without hyalocytes, but with the hyalocytes, 100 ,g/ml of bevacizumab was required to decrease the percentage of viable HRECs stimulated by VEGF. Fenofibrate, at 5 ,g/ml, decreased the viability of HRECs stimulated by IL-1, and VEGF without hyalocytes but could not decrease the viability of HRECs cocultured with hyalocytes. Dexamethasone, at 50 ,g/ml, decreased the viability of HRECs stimulated by IL-1,, IL-1,, IL-6 and VEGF without hyalocytes but could not decrease the viability of HRECs cocultured. Conclusions:, Coculturing HRECs with vitreous-derived hyalocytes depressed the effects of cytokines, bevacizumab, fenofibrate and dexamethasone. This suggests that the vitreal hyalocytes may play a role in pathogenic endothelial cell proliferation in vivo. Future studies to better understand this pathobiology should utilize coculture systems of HRECs and vitreal hyalocytes. [source] Inhibition of human vascular endothelial cells proliferation by terbinafineINTERNATIONAL JOURNAL OF CANCER, Issue 1 2004Pei-Yin Ho Abstract We have demonstrated previously that terbinafine (TB), an oral antifungal agent used in the treatment of superficial mycosis, suppresses proliferation of various cultured human cancer cells in vitro and in vivo by inhibiting DNA synthesis and activating apoptosis. In our study, we further demonstrated that TB at a range of concentrations (0,120 ,M) dose-dependently decreased cell number in cultured human umbilical vascular endothelial cells (HUVEC). Terbinafine was not cytotoxic at a concentration of 120 ,M, indicating that it may have an inhibitory effect on the cell proliferation in HUVEC. The TB-induced inhibition of cell growth rate is reversible. [3H]thymidine incorporation revealed that TB reduced the [3H]thymidine incorporation into HUVEC during the S-phase of the cell-cycle. Western blot analysis demonstrated that the protein levels of cyclin A, but not cyclins B, D1, D3, E, CDK2 and CDK4, decreased after TB treatment. The TB-induced cell-cycle arrest in HUVEC occurred when the cyclin-dependent kinase 2 (CDK2) activity was inhibited just as the protein level of p21 was increased and cyclin A was decreased. Pretreatment of HUVEC with a p21 specific antisense oligonucleotide reversed the TB-induced inhibition of [3H]thymidine incorporation. Taken together, these results suggest an involvement of the p21-associated signaling pathway in the TB-induced antiproliferation in HUVEC. Capillary-like tube formation and chick embryo chorioallantoic membrane (CAM) assays further demonstrated the anti-angiogenic effect of TB. These findings demonstrate for the first time that TB can inhibit the angiogenesis. © 2004 Wiley-Liss, Inc. [source] | ||||||||||||||||