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Arterial Wall (arterial + wall)

Distribution by Scientific Domains

Medical Sciences	83%
Life Sciences	13%

Distribution within Medical Sciences

General & Internal Medicine	15%
Cardiovascular Disease	6%
16 Other Subdomains	64%

Selected Abstracts

GENETIC INFLUENCES ON THE ARTERIAL WALL

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2007
Bronwyn Kingwell
SUMMARY 1Arterial stiffness, which has independent predictive value for cardiovascular events, seems to have a genetic component, largely independent of the influence of blood pressure and other cardiovascular risk factors. 2In animal models of essential hypertension (stroke-prone spontaneously hypertensive rats and spontaneously hypertensive rats), structural modifications of the arterial wall include an increase in the number of elastin,smooth muscle cell connections and smaller fenestrations of the internal elastic lamina, possibility leading to redistribution of the mechanical load towards elastic materials. These modifications may give rise to mechanisms explaining why changes in arterial wall material accompanying wall hypertrophy in these animals are not associated with an increase in arterial stiffness. 3In monogenic connective tissue diseases (Marfan, Williams and Ehlers,Danlos syndromes) and the corresponding animal models, precise characterization of the arterial phenotype makes it possible to determine the influence of abnormal, genetically determined, wall components on arterial stiffness. 4Such studies have highlighted the role of extracellular matrix signalling in the vascular wall and have shown that elastin and collagen not only display elasticity or rigidity, but are also involved in the control of smooth muscle cell function. 5These data provide strong evidence that arterial stiffness is affected by the amount and density of stiff wall material and the spatial organization of that material. [source]

Baroreflex Sensitivity of an Arterial Wall During Rotary Blood Pump Assistance

ARTIFICIAL ORGANS, Issue 9 2009
Tomoyuki Yambe
Abstract It is well known that the baroreflex system is one of the most important indicators of the pathophysiology in hypertensive patients. We can check the sensitivity of the baroreflex by observing heart rate (HR) responses; however, there is no simple diagnostic method to measure the arterial behavior in the baroreflex system. Presently, we report the development of a method and associated hardware that enables the diagnosis of baroreflex sensitivity by measuring the responses of both the heart and the artery. In this system, the measurements are obtained by monitoring an electrocardiogram and a pulse wave recorded from the radial artery or fingertip. The arterial responses were measured in terms of the pulse wave velocity (PWV) calculated from the pulse wave transmission time (PTT) from the heart to the artery. In this system, the HR change corresponding to the blood pressure change in time series sequence was observed. Slope of the changes in blood pressure and HR indicated the sensitivity of the baroreflex system of the heart. This system could also measure the sensitivity of the baroreflex system of an artery. Changes in the PWV in response to the blood pressure changes were observed. Significant correlation was observed in the time sequence between blood pressure change and PWV change after calculating the delay time by cross-correlation. The slope of these parameter changes was easily obtained and it demonstrated the sensitivity of the baroreflex system of an artery. We evaluated this method in animal experiments using rotary blood pump (RBP) with undulation pump ventricular assist device, and PTT elongation was observed in response to increased blood pressure with RBP assistance. Furthermore, when tested clinically, decreased sensitivity of the baroreflex system in hypertensive patients was observed. This system may be useful when we consider the ideal treatment and follow-up of patients with hypertension. [source]

Assessment of Carotid Compliance Using Real Time Vascular Ultrasound Image Analysis in Marfan Syndrome

ECHOCARDIOGRAPHY, Issue 4 2009
Anatoli Kiotsekoglou M.D.
Background: Fibrillin-1 deficiency, dysregulated cytokine transforming growth factor-,, and increased collagen deposition related to fibrillin-1 gene mutations could predispose to impaired carotid compliance (CC) in Marfan syndrome (MFS). We sought to detect any alterations in CC using the vascular image analysis system (VIA). Methods and Results: Thirty-two MFS patients, 20 men and 12 women (mean age 34.2 ± 12.05 years), and 29 controls matched for age, sex, and body surface area (BSA) were recruited. The entire length of each carotid system was initially scanned longitudinally using a 14 MHz linear transducer. Then, a stereotactic clamp held the transducer in contact with the carotid artery. Arterial diameter changes during the cardiac cycle were recorded for 1 minute from both right (RCCA) and left common carotid arteries (LCCA) separately using the VIA system. RCCA and LCCA compliance and distensibility measurements were significantly reduced in MFS patients when compared to controls, P < 0.05. RCCA and LCCA intima-media thickness did not differ between patients and controls, P > 0.05. MFS diagnosis and age were associated with reduced CC in both carotid arteries after adjusting for variables such as, sex, BSA, heart rate, beta-blockade, intima-media thickness, and aortic root size. Conclusions: Our findings showed a reduction in CC in adult patients with MFS. This could be attributed to fibrillin-1 deficiency resulting in structural abnormalities in the carotid arterial wall. [source]

Pathology of lethal peripartum broad ligament haematoma in 31 Thoroughbred mares

EQUINE VETERINARY JOURNAL, Issue 6 2010
T. UENO
Summary Reasons for performing study: Broad ligament haemorrhage in peripartum mares is a life-threatening disease and there are few reports on the aetiology and pathogenesis of broad ligament haematoma. Objectives: To obtain information regarding the sites for the early diagnosis and pathogenesis of broad ligament haematoma of mares. Methods: Thirty-one mares that died of broad ligament haematoma peripartum were examined pathologically for bleeding sites. The arterial distribution of 5 young mares with several parities served as negative controls. Results: Age and/or multiparity were the predisposing factors for the disease. Arterial injuries were most commonly observed in the uterine artery (24 of 31 mares). Among these, the proximal uterine artery that lies within 15 cm of the bifurcation of the iliac artery was the most frequent site for rupture (18 mares). The lesions occurred preferentially at the bifurcations, lateral part of curvatures and abrupt flexures of the artery. The morphology of the injuries was classified into 3 types: ruptures with and without longitudinal fissures, and transections. Histologically, the arterial wall adjacent to the rupture showed atrophy of smooth muscle cells with fibrosis of the tunica media and disruption and/or calcification of the internal elastic lamina. Conclusions: Arterial injuries that led to broad ligament haematoma in peripartum mares occurred most frequently in the proximal uterine artery, and atrophy of smooth muscle cells with fibrosis of the arterial wall was as one of the predisposing factors in aged and multiparous mares. Potential relevance: Monitoring small aneurysms, mural tearing, medial fibrosis at the proximal uterine artery by transrectal echography could provide useful information for the early diagnosis and possible prevention of broad ligament haematoma of peripartum mares. [source]

Aminoguanidine prevents arterial stiffening in a new rat model of type 2 diabetes

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 8 2006
K.-C. Chang
Abstract Background, Formation of advanced glycation end-products (AGEs) on collagen within the arterial wall may be responsible for the development of diabetic vascular injury. This study focused on investigating the role of aminoguanidine (AG), an inhibitor of AGE formation, in the prevention of noninsulin-dependent diabetes mellitus (NIDDM)-derived arterial stiffening and cardiac hypertrophy in rats. Materials and methods, The NIDDM was induced in male Wistar rats, which were administered intraperitoneally with 180 mg kg,1 nicotinamide (NA) 30 min before an intravenous injection of 50 mg kg,1 streptozotocin (STZ). After induction of diabetes mellitus type 2, animals receiving daily peritoneal injections with 50 mg kg,1 AG for 8 weeks were compared with the age-matched, untreated, diabetic controls. Results, After exposure to AG, the STZ-NA diabetic rats had improved aortic distensibility, as evidenced by 18·8% reduction of aortic characteristic impedance (P < 0·05). Treatment of the experimental syndrome with AG also resulted in a significant increase in wave transit time (+23·7%, P < 0·05) and a decrease in wave reflection factor (,26·6%, P < 0·05), suggesting that AG may prevent the NIDDM-induced augmentation in systolic load of the left ventricle. Also, the glycation-derived modification on aortic collagen was found to be retarded by AG. The diminished ratio of left ventricular weight to body weight suggested that prevention of the diabetes-related cardiac hypertrophy by AG may correspond to the drug-induced decline in aortic stiffening. Conclusions, Long-term administration of AG to the STZ-NA diabetic rats imparts significant protection against the NIDDM-derived impairment in vascular dynamics, at least partly through inhibition of the AGE accumulation on collagen in the arterial wall. [source]

Endothelial dysfunction in Buerger's disease and its relation to markers of inflammation

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2006
M. Joras
Abstract Background, Buerger's disease (BD) is a segmental occlusive vascular disease. The aim of this study was to detect functional changes in brachial artery and asymptomatic morphological changes in extra-cranial carotid arteries not affected by the disease process and to assess markers of inflammation and endothelial damage. Materials and methods, Fourteen patients in the remission phase of BD and the same number of age- and sex-matched healthy controls were included in the study. The capability of endothelium-dependent (flow-mediated) and endothelium-independent dilation of the brachial artery and intima-media thickness of the carotid arteries were measured using high-resolution ultrasound. Laboratory parameters of endogenous fibrinolytic activity, inflammation and endothelial dysfunction were also measured. Results, Patients with BD had a diminished capability of endothelium-dependent vasodilation and higher levels of some circulating markers of inflammation, such as leukocytes, C-reactive protein, intercellular adhesion molecule-1 and E-selectin. Intercellular adhesion molecule-1 levels were related to some of the inflammatory markers (sedimentation rate, C-reactive protein, ,2-globulins and fibrinogen), while E-selectin was correlated with decreased endogenous blood fibrinolytic activity. Endothelium-dependent vasodilation was in negative correlation with the relative share of neutrophil granulocytes. There were no significant differences in intima-media thickness between patients with BD and controls. Conclusions, Our study has expressed generalized functional arterial disorder in patients with BD not accompanied by any measurable morphological changes of the carotid arterial wall. Functional deterioration of brachial artery could be related to increased levels of various inflammatory markers , the process which is most probably the basic pathogenetic mechanism of the disease. [source]

Association of serum sialic acid and MMP-9 with lipids and inflammatory markers

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2000
Kalela
Background Inflammation of the arterial wall has emerged to be an important contributor to the process of atherosclerosis, the major cause of coronary heart disease. Several factors are currently under investigation as inflammatory markers of atherosclerosis. Serum sialic acid and matrix metalloproteinase-9 may provide such markers. We studied their association with the lipid profile and with the inflammatory markers C-reactive protein and leukocyte count in a clinically healthy population of men. Materials and methods Cardiovascular risk-related laboratory tests were carried out in 65 consecutive male employees in connection with an occupational health survey in 1996. The subjects were divided into tertiles on the basis of serum sialic acid or matrix metalloproteinase-9 concentration. Results In a stepwise polychotomous logistic regression model adjusting for coronary heart disease risk factors, serum sialic acid concentration was not associated with markers of inflammation but rather with the lipid risk factors of atherosclerosis: inversely with HDL cholesterol (OR = 0.081, 95% CI 0.0068,0.97) and positively with total cholesterol (OR = 2.4, 95% CI 1,5.6). Matrix metalloproteinase-9 levels had a significant positive correlation with the leukocyte count (OR = 2.3, 95% CI 1.4,4). Conclusions Serum sialic acid does not appear to be an indicator of inflammation but is somehow connected with the level of total and HDL cholesterol. Serum matrix metalloproteinase-9 may provide a useful marker of inflammation because it correlates with the leukocyte count and is not associated with the lipid profile. [source]

Intima-media thickness of radial artery is associated with early access failure in hemodialysis patients

HEMODIALYSIS INTERNATIONAL, Issue 1 2005
Y.O. Kim
Objective:,We have reported that intimal hyperplasia, which is the pathologic change of the radial artery, is associated with early failure of arteriovenous fistula (AVF) in hemodialysis (HD) patients (Am J Kidney Dis, 41:422,428, 2003). Intima-media thickness (IMT), which represents the whole thickness of arterial wall, can be easily measured by ultrasonography, unlike intima thickness. This study was performed to investigate the impact of IMT of radial artery on early failure of AVF in HD patients. Methods:,Ninety HD patients undergoing radiocephalic AVF operation were included in this study. The AVF was constructed in an end vein,to,side artery fashion at the wrist by one vascular surgeon. During the operation, 10-mm long partial arterial walls were removed with elliptical form for microscopic analysis. Specimens were stained with trichrome and examined by a pathologist blinded to the clinical data. AVF patency was prospectively followed up for 1 year after the operation. Results:,Mean age of the patients was 56 ± 13 years and the number of females was 44 (48.9%). Mean IMT was 430 ± 132 ,m (133,760 ,m). Of the total 90 patients, 31 patients (34.4%) had AVF failure within 1 year after the operation. Mean IMT was higher in the failed group (n = 31) than in patent group (n = 59)(486 ± 130 ,m vs. 330 ± 178 ,m, p = 0.004). Using a threshold of 500 ,m of IMT, AVF patency rate was compared between these two groups using Kaplan-Meier method with log rank test. The AVF patency rate within 1 year after the operation was higher in patients with IMT , 500 ,m (n = 26) than in patients with IMT < 500 ,m (n = 64)(p < 0.001). The patients with IMT , 500 ,m were older and had higher incidence of diabetes mellitus, compared to the patients with IMT < 500 ,m. There was no difference in sex, smoking, hypertension, total cholesterol and albumin levels between the two groups. Conclusion:,Our data suggest that increased intima-media thickness of radial artery is associated with early failure of radiocephalic arteriovenous fistula in hemodialysis patients. [source]

Vaccines modulating lipoprotein autoimmunity as a possible future therapy for cardiovascular disease

JOURNAL OF INTERNAL MEDICINE, Issue 3 2009
J. Nilsson
Abstract. Current strategies for prevention of cardiovascular disease focus on risk factor intervention. Although these have been proven both safe and effective results from randomized clinical trials suggest that it is difficult to achieve relative risk reductions exceeding 40% with this approach. To further improve efficacy future therapies must aim at targeting the actual disease process in the arterial wall. Emerging evidence have identified an important role of the immune system in atherosclerosis and suggest that modulation of autoimmune responses against oxidized LDL and other antigens in the atherosclerotic plaque represent one possible new approach to disease prevention. Oxidized LDL is targeted by both antibody-mediated and cellular immune responses and as much as 10% of the T cells in atherosclerotic plaques are oxidized LDL-specific. Immune activation in the atherosclerotic plaque is primarily of the pro-inflammatory Th1-type and inhibition Th1 immunity reduces atherosclerosis in experimental animals. Atherosclerosis vaccines based on antigens derived from LDL have been developed to modulate these processes. Their mechanisms of action remain to be full characterized but may involve expression of protective antibodies that facilitate the removal of oxidized LDL and antigen-specific regulatory T cells that counteract Th1 autoimmunity against oxidized LDL. In this review we will discuss the possibilities and challenges encountering the translation of immune-modulatory therapy for atherosclerosis from the experimental stage into the clinic. [source]

Progenitor cell trafficking in the vascular wall

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2009
M. HRISTOV
Summary., Adult endothelial as well as smooth muscle progenitor cells are engaged in the complex pathophysiology of atherosclerosis including primary remodeling with development and progression of atherosclerotic plaques as well as secondary complications associated with ischemia, endothelial damage, neointimal growth and transplant arteriosclerosis. These adult vascular precursor cells correspond to similar embryonic stem cell-derived progeny and are primarily located in bone marrow and peripheral blood. Recently, specific investigation on their recruitment emerged as a novel fundamental in the pathogenesis of arterial remodeling, plaque stability and angiogenesis. This multifaceted process of mobilization and homing is regulated by numerous chemokines, adhesion molecules and growth factors that guide and control the trafficking of vascular progenitor cells to the arterial wall after injury or during ischemia. [source]

Plaque progression and regression in atherothrombosis

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2007
B. IBANEZ
Summary., Atherosclerotic disease is a pathological process characterized by the deposition of lipid and other blood-borne material within the arterial wall. The deposition of these materials and the subsequent thickening of the wall may significantly compromise the vessel lumen. Atherosclerosis is a diffuse disease with focal clinical manifestations that are the consequence of thrombotic complications on disrupted atherosclerotic lesions. Until recently, atherosclerosis development was envisaged as an incessant progressing process; however, new evidence has shown that atherosclerotic plaque homeostasis is not necessarily a constantly progressing process. There are many data showing that atherosclerotic plaque formation can be slowed, stopped or even reversed. Comprehension of the underlying mechanisms involved in the homeostasis of atherosclerotic plaque (progression/regression) should allow the development of interventions enhancing the regression pathway. Novel imaging technology has allowed the accurate evaluation of plaque progression, vital in the assessment of the efficacy of interventions. In this review we discuss the processes involved in the formation and progression of atherosclerotic lesions, the triggers for plaque disruption, as well as new therapies. We also deal with the potential pathways of plaque regression, as well as tools for accurate serial atherosclerotic quantification. [source]

Circumferential strain in the wall of the common carotid artery: Comparing displacement-encoded and cine MRI in volunteers

MAGNETIC RESONANCE IN MEDICINE, Issue 1 2008
Alexander P. Lin
The walls of conduit arteries undergo cyclic stretching from the periodic fluctuation of arterial pressure. Atherosclerotic lesions have been shown to localize to regions of excessive stretching of the arterial wall. We employed a displacement encoding with stimulated echoes (DENSE) sequence to image the motion of the common carotid artery wall and map the two-dimensional (2D) circumferential strain. The sequence utilizes a fully-balanced steady-state free-precession (SSFP) readout with 0.60 mm in-plane resolution. Preliminary results in volunteers at 1.5T (N = 4) and 3.0T (N = 17) are compared to measurements of the lumen circumference from cine images. The agreement between the two independent measurements at both field strengths (P , 0.001) supports the use of DENSE as a means to map the pulsatile strain in the carotid artery wall. Magn Reson Med 60:8,13, 2008. © 2008 Wiley-Liss, Inc. [source]

Mucormycotic pseudoaneurysm of the common carotid artery with tracheal involvement

MYCOSES, Issue 4 2008
S. Hashemzadeh
Summary Mucormycosis is an emerging and fatal fungal infection. A high index of suspicion and the knowledge of its potential manifestations are essential for early diagnosis. We describe a patient with acute lymphoblastic leukaemia (L2 subtype) who developed a neck mass following a course of induction chemotherapy. Doppler ultrasonography and angiography of the neck revealed a pseudoaneurysm of the right common carotid artery. The patient then developed haemoptysis. Surgical exploration revealed a necrotic right common carotid artery with anteromedial pseudoaneurysm and adjacent tracheal wall perforation. Local debridement and tracheal repair were performed. Nonseptate hypheal invasion (mucormycosis) was found on the microscopic examination of the excised arterial wall. A subsequent recurrence of pseudoaneurysm was treated with local surgical debridement and intravenous amphotericin B (Fungizone) administration. Although rare, clinicians should be aware of these possible presenting features of mucormycosis as early diagnosis and treatment may potentially improve the survival. [source]

MRI of atherosclerosis in clinical trials

NMR IN BIOMEDICINE, Issue 6 2006
Chun Yuan
Abstract Magnetic resonance imaging (MRI) of the arterial wall has emerged as a viable technology for characterizing atherosclerotic lesions in vivo, especially within carotid arteries and other large vessels. This capability has facilitated the use of carotid MRI in clinical trials to evaluate therapeutic effects on atherosclerotic lesions themselves. MRI is specifically able to characterize three important aspects of the lesion: size, composition and biological activity. Lesion size, expressed as a total wall volume, may be more sensitive than maximal vessel narrowing (stenosis) as a measure of therapeutic effects, as it reflects changes along the entire length of the lesion and accounts for vessel remodeling. Lesion composition (e.g. lipid, fibrous and calcified content) may reflect therapeutic effects that do not alter lesion size or stenosis, but cause a transition from a vulnerable plaque composition to a more stable one. Biological activity, most notably inflammation, is an emerging target for imaging that is thought to destabilize plaque and which may be a systemic marker of vulnerability. The ability of MRI to characterize each of these features in carotid atherosclerotic lesions gives it the potential, under certain circumstances, to replace traditional trials involving large numbers of subjects and hard end-points , heart attacks and strokes , with smaller, shorter trials involving imaging end-points. In this review, the state of the art in MRI of atherosclerosis is presented in terms of hardware, image acquisition protocols and post-processing. Also, the results of validation studies for measuring lesion size, composition and inflammation will be summarized. Finally, the status of several clinical trials involving MRI of atherosclerosis will be reviewed. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Mycotic pseudoaneurysm following a kidney transplant: A case report and review of the literature

PEDIATRIC TRANSPLANTATION, Issue 5 2009
Ignacio Osmán
Abstract:, Vascular complications represent a significant cause of morbidity and mortality following a kidney transplant. Pseudoaneurysms are rare, occurring in approximately 1% of cases. We present a 15-yr-old patient who received a kidney transplant in the right iliac fossa. Thirty-six days following the transplant, the patient was admitted to the hospital because of a marked increase in serum creatinine levels, arterial hypertension, scrotal edema, and lower right limb pain. The patient did not present fever or raised inflammatory markers. A pseudoaneurysm was diagnosed by means of a Doppler echography and a CT. By a selective arteriography of the right iliac artery, we placed a 8 × 5 cm stent to isolate the pseudoaneurysm, due to the high risk of an extensive defect occurring in the arterial wall. Forty-eight h later the patient underwent transplant nephrectomy. Seven days following surgery, the patient experienced febrile syndrome and therefore another CT was carried out which showed a large abscess around the stent. So we decided to perform another intervention in order to drain this abscess. Due to the extensive loss of the arterial wall where the prosthesis was largely exposed, we ligated the common iliac and external iliac arteries, removed the prosthesis and performed a femoro-femoral bypass with the usual subcutaneous positioning of the prosthesis (separate from surgical site). The stent and mural thrombus were sent for culture analysis and Candida albicans was observed. The diagnosis of a pseudoaneurysm in these types of patients continues to be considered as a surgical emergency by the majority of authors. Transplantectomy is the most frequently used treatment technique. Positioning a stent prior to transplantectomy avoids ligature of the iliac artery in the majority of cases. [source]

In Vivo Optical Analysis of Quantitative Changes in Collagen and Elastin During Arterial Remodeling,

PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2005
Alexander Christov
ABSTRACT Altered collagen and elastin content correlates closely with remodeling of the arterial wall after injury. Optical analytical approaches have been shown to detect qualitative changes in plaque composition, but the capacity for detection of quantitative changes in arterial collagen and elastin content in vivo is not known. We have assessed fluorescence spectroscopy for detection of quantitative changes in arterial composition in situ, in rabbit models of angioplasty and stent implant. Fluorescence emission intensity (FEI) recorded at sites remote from the primary implant site was correlated with immunohistochemical (IH) analysis and extracted elastin and collagen. FEI was significantly decreased (P < 0.05) after treatment with anti-inflammatory agents, and plaque area decreased on comparison with saline-treated rabbits after stent implant or angioplasty (P, 0.013). Excellent correlations for FEI with elastin and collagen I, III and IV content measured by IH (R2, 0.961) analysis were detected by multiple regression (MR) analysis. Good correlations also were found for FEI with elastin and collagen measured by high-performance liquid chromatography; MR analysis provided highly predictive values for collagen and elastin (R2, 0.994). Fluorescence spectroscopic analysis detects quantitative compositional changes in arterial connective tissue in vivo, demonstrating changes at sites remote from primary angioplasty and stent implant sites. [source]

Crataegus tanacetifolia leaf extract prevents L-NAME-induced hypertension in rats: a morphological study

PHYTOTHERAPY RESEARCH, Issue 1 2006
Z. Çelebi Koçyõldõz
Abstract Crataegus (hawthorn) has long been used as a folk medicine all around the world. Most of the studies with Crataegus species focus on effects on heart failure and cardiovascular disease. The pharmacological effects of Crataegus have been attributed mainly to the content of flavonoids, procyanidin, aromatic acid and cardiotonic amines. The present study investigated the blood pressure and the structure of the coronary arterial wall of L-NAME-induced hypertensive rats given an aqueous leaf extract of C. tanacetifolia (100 mg/kg), for 4 weeks via gavage. It was observed that C. tanacetifolia, especially the hyperoside fraction, prevented L-NAME-induced hypertension in rats and had beneficial effects on the cardiovascular system. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Proteomic analysis of human vessels: Application to atherosclerotic plaques

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 6 2003
Mari Carmen Duran
Abstract Atherosclerosis is a chronic disease that affects medium and large arteries. This process originates from the interaction between cells of the arterial wall, lipoproteins and inflammatory cells, leading to the development of complex lesions or plaques that protrude into the arterial lumen. Plaque rupture and thrombosis result in acute clinical complications such as myocardial infarction and stroke. Owing to the heterogeneous cellular composition of the plaques, a proteomic analysis of the whole lesion is not appropriate. Therefore, we have studied the proteins secreted by human carotid atherosclerotic plaques, obtained by endarterectomy. Normal artery segments and different regions of the surgical pieces (noncomplicated plaque, complicated plaque with thrombus) were cultured in protein-free medium and the secreted proteins (supernatants) analyzed by two-dimensional gel electrophoresis. Normal artery segments secreted a moderate number of proteins (42 spots). However in the two-dimensional (2-D) gels (pH 3,10) of segments bearing a plaque, the number of spots increased markedly (154). The number of spots also increased (202) in the 2-D gels of artery segments with a ruptured plaque and thrombus. Thus, the more complicated the lesion, the higher the number of secreted proteins, suggesting the production of specific proteins relating to the complexity of the atherosclerotic lesion. [source]

Intravascular ultrasound imaging of the pulmonary arteries in primary pulmonary hypertension

RESPIROLOGY, Issue 1 2000
Takaaki Nakamoto
Objective: Intravascular ultrasound has the unique ability to provide cross-sectional images of the arterial wall. This study examined intravascular ultrasound (IVUS) images of the proximal pulmonary arteries in primary pulmonary hypertension (PPH). Methodology: Study 1: Specimens from four patients who had died of PPH (in vitro PPH group) were compared with those of three patients who had died of subarachnoid haemorrhage but had no evidence of cardiopulmonary disease (in vitro control group). Three-centimetre segments of the following levels were examined by IVUS: pulmonary trunk, eight secondary branch arteries of the upper, middle, and lower lobes of both lungs, and the thoracic descending aorta. Study 2: Four patients with PPH (in vivo PPH group) and five patients without pulmonary hypertension and no evidence of cardiopulmonary disease (in vivo control group) were examined. The IVUS images of the apical segmental artery of the right upper lobe and the descending branch of the right pulmonary artery were studied. Results: Echographic examination of formalin-fixed preparations of secondary branch sections of the pulmonary artery failed to show a clear three-layer structure in the in vitro control group (24 preparations), but a distinct three-layer structure and increased vessel wall thickness were observed in the in vitro PPH group (32 preparations). Similar findings were obtained in the in vivo study. The mean echo density of the proximal pulmonary arterial wall correlated well with the mean pulmonary arterial pressure (mPA) in the in vitro PPH, and also correlated with the mPA in the in vivo study (r = 0.960, P < 0.0001). The echo intensity of secondary branch sections of the pulmonary artery was higher in the in vitro PPH group than in the in vitro control group (180.5 ± 27.0 vs 132.5 ± 26.7 counts, P < 0.001); similar results were obtained in the in vivo study (144.7 ± 23.4 vs 85.0 ± 14.3 counts, P < 0.01). Conclusions: These results suggest that the histological changes detected in the pulmonary artery walls in the PPH group were responsible for the increased echo intensity. [source]

Local matrix metalloproteinase 2 gene knockdown in balloon-injured rabbit carotid arteries using nonviral-small interfering RNA transfection

THE JOURNAL OF GENE MEDICINE, Issue 1 2009
Hanna Hlawaty
Abstract Background Small interfering RNA (siRNA) delivery is a promising approach for the treatment of cardiovascular diseases. Matrix metalloproteinase (MMP) 2 over-expression in the arterial wall has been implicated in restenosis after percutaneous coronary intervention, as well as in spontaneous atherosclerotic plaque rupture. We hypothesized that in vivo local delivery of siRNA targeted at MMP2 (MMP2-siRNA) in the balloon-injured carotid artery of hypercholesterolemic rabbits may lead to inhibition of MMP2 expression. Methods Two weeks after balloon injury, 5 µmol/l of Tamra-tagged MMP2-siRNA, scramble siRNA or saline was locally injected in the carotid artery and incubated for 1 h. Results Fluorescent microscopy studies showed the circumferential uptake of siRNA in the superficial layers of neointimal cells. MMP2 mRNA levels, measured by the real-time reverse transcriptase-polymerase chain reaction, was decreased by 79 ± 25% in MMP2-siRNA- versus scramble siRNA-transfected arteries (p < 0.05). MMP2 activity, measured by gelatin zymography performed on the conditioned media of MMP2-siRNA versus scramble siRNA transfected arteries, decreased by 53 ± 29%, 50 ± 24% and 46 ± 14% at 24, 48 and 72 h, respectively (p < 0.005 for all). No effect was observed on MMP9, pro-MMP9 and TIMP-2 levels. Conclusions The results obtained in the present study suggest that significant inhibition of gene expression can be achieved with local delivery of siRNA in the arterial wall in vivo. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Elevated matrilysin levels in bronchoalveolar lavage fluid do not distinguish idiopathic pulmonary fibrosis from other interstitial lung diseases,

APMIS, Issue 8 2007
KIRSI VUORINEN
Microarray studies have shown that matrilysin or matrix metalloproteinase (MMP)-7 is highly upregulated in the lungs of patients with idiopathic pulmonary fibrosis (IPF), but MMP-7 protein expression has not been systematically compared between IPF and other interstitial lung diseases. MMP-7 levels in bronchoalveolar lavage fluid (BALF) were compared to corresponding samples from nonspecific interstitial pneumonia (NSIP), sarcoidosis, and healthy controls. MMP-7 levels in the BALF were determined by ELISA and localization of MMP-7 in the lung tissue by immunohistochemistry. MMP-7 was similarly elevated in the BALF of all these disorders compared to healthy controls (p=0.007). Even control subjects with prolonged cough displayed a tendency towards elevated MMP-7 expression. There was a negative correlation between BALF MMP-7 levels and forced expiratory vital capacity (r=,0.348, p=0.02, n=42). In IPF lung, MMP-7 immunoreactivity appeared predominantly in the fibrotic parenchyma and arterial wall. In sarcoidosis and NSIP, prominent MMP-7 immunoreactivity was found in areas of inflammation. These results demonstrate that elevated BALF MMP-7 is not restricted to IPF alone but is also observed in other interstitial lung diseases and cannot be used as a differential diagnostic marker for IPF. [source]

Inflammation and bone resorption as independent factors of accelerated arterial wall thickening in patients with rheumatoid arthritis

ARTHRITIS & RHEUMATISM, Issue 11 2003
Mayumi Nagata-Sakurai
Objective We recently reported that rheumatoid arthritis (RA) patients had increased intima-media thickness (IMT) of the common carotid artery (CCA). The present longitudinal study was performed to determine whether the change in arterial thickness was accelerated in RA patients and to determine which factor was important in the progression of arterial wall changes. Methods We studied 62 female RA patients with stable disease activity and 63 healthy female controls. IMT of the CCA was measured twice by high-resolution B-mode ultrasonography. The second examination was performed 18,36 months after the first, and changes were expressed as millimeters of increase per year. Baseline examinations included blood markers of inflammation and urinary calcium excretion (expressed as the calcium-to-creatinine ratio). Results RA patients showed a significantly greater increase in IMT of the CCA compared with controls. In univariate analyses of the RA patient data, the C-reactive protein (CRP) level correlated with the increase in CCA IMT. Other markers of inflammation (the erythrocyte sedimentation rate and white blood cell and platelet counts) also showed significant positive associations with the annual increase in CCA IMT in multiple regression models when adjusted for age, smoking status, blood pressure, and serum cholesterol level. The urinary calcium-to-creatinine ratio was also significantly associated with an increase in CCA IMT. Moreover, both the CRP level and the urinary calcium-to-creatinine ratio were significantly and independently associated with the increase in IMT of the CCA. Conclusion Patients with RA have a higher rate of increase in thickening of the arterial wall. Inflammation and calcium mobilization are factors closely associated with the accelerated arterial wall changes. [source]

Regulation of coenzyme Q biosynthesis and breakdown

BIOFACTORS, Issue 1-4 2003
Gustav Dallner
Abstract All animal cells synthesize sufficient amounts of coenzyme Q (CoQ) and the cells also possess the capacity to metabolize the lipid. The main product of the metabolism is an intact ring with a short carboxylated side chain which glucuronidated in the liver and excreted mainly into the bile (Nakamura et al., Biofactors 9 (1999), 111,119). In other cells CoQ is phosphorylated, transferred into the blood and excreted through the urine. The biosynthesis of this lipid is regulated by nuclear receptors. PPAR, is not required for the biosynthesis, or induction upon cold exposure, but it is necessary for the elevated CoQ synthesis during peroxisomal induction. RXR, is involved in the basal synthesis of CoQ and also in the increased synthesis upon cold treatment but is not required for peroxisomal induction. Dietary CoQ in human appear in the blood and it is taken up by mononuclear but not polynuclear cells. The former cells display a specific phospholipid modification, an increase of arachidonic acid content. In monocytes the CoQ administration leads to a significant decrease of the ,2-integrin CD11b and the complement receptor CD35. CD11b is one of the adhesion factors regulating the entry of these cells into the arterial wall which demonstrates that the anti-atherogenic effect of CoQ is mediated by other mechanisms beside its antioxidant protection. [source]

Can coenzyme Q10 improve vascular function and blood pressure?

BIOFACTORS, Issue 1-4 2003
Potential for effective therapeutic reduction in vascular oxidative stress
Abstract Coenzyme Q10 (CoQ) is an endogenously synthesised compound that acts as an electron carrier in the mitochondrial electron transport chain. The presence of adequate tissue concentrations of CoQ may be important in limiting oxidative and nitrosative damage in vivo. Oxidative and nitrosative stress are likely to be elevated in conditions such as diabetes and hypertension. In these conditions elevated oxidative and nitrosative stress within the arterial wall may contribute to increased blood pressure and vascular dysfunction. The major focus of this review is the potential of CoQ to improve vascular function and lower blood pressure. Although there is substantial indirect support for the putative mechanism of effect of CoQ on the vascular system, to date there is little direct support for an effect of CoQ on in vivo markers of oxidative or nitrosative stress. The limited data available from studies in animal models and from human intervention studies are generally consistent with a benefit of CoQ on vascular function and blood pressure. The observed effects of CoQ on these endpoints are potentially important therapeutically. However, before any firm clinical recommendations can be made about CoQ supplementation, further intervention studies in humans are needed to investigate the effects of CoQ on vascular function, blood pressure and cardiovascular outcomes. The particularly relevant groups of patients for these studies are those with insulin resistance, type 2 diabetes, hypertension and the metabolic syndrome. [source]

Fibrosis and Stenosis of the Long Penetrating Cerebral Arteries: the Cause of the White Matter Pathology in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy

BRAIN PATHOLOGY, Issue 4 2004
Qing Miao MSc
In cerebral autosomal dominant arteriopathy with subcortical infarcts and leuco-encephalopathy (CADASIL) the vascular smooth muscle cells are destroyed and granular osmiophilic material is deposited followed by fibrosis of the arterial wall. To verify whether true stenosis of the fibrotic white matter arteries is a key pathogenic event in CADASIL, we analyzed the thickness of walls (expressed as sclerotic index) and luminal diameters of penetrating arterioles in both grey matter and white matter of four CADASIL patients due to the C475T (R133C) mutation in the Notch3 gene and in 9 age-matched controls. We also reconstructed 9 arterioles from 1000 serial sections in two CADASIL patients. The thickness of the arteriolar walls in both grey matter and white matter was significantly increased in the CADASIL patients compared with controls. Furthermore, in CADASIL patients the arteriolar walls were significantly thicker in the white matter than in the grey matter. The distribution curve of arteriolar internal diameters in CADASIL patients shifted towards smaller sizes. In serial sections, the marked increase in the thickness of the white matter penetrating arterioles or their branches did not occur until the internal diameters had decreased to about 20 to 30 ,m and external diameters to about 100 to 130 ,m. In conclusion, long penetrating arterioles and their branches supplying subcortical structures in CADASIL are stenosed and their walls are thickened. This conforms to the abundance of infarcts and primary ischemic damage in CADASIL patients' white matter. [source]

P2 receptors: new potential players in atherosclerosis

BRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2002
Francesco Di Virgilio
Atherosclerosis is a focal inflammatory disease of the arterial wall. It starts with the formation of fatty streaks on the arterial wall that evolve to form a raised plaque made of smooth muscle cells (SMCs), and infiltrating leukocytes surrounding a necrotic core. The pathogenesis of the atherosclerotic lesion is incompletely understood, but it is clear that a dysfunction of the endothelium, recruitment and activation of inflammatory cells and SMC proliferation have a pivotal role. Over recent years receptors for extracellular nucleotides, the P2 receptors, have been recognized as fundamental modulators of leukocytes, platelets, SMCs and endothelial cells. P2 receptors mediate chemotaxis, cytokine secretion, NO generation, platelet aggregation and cell proliferation in response to accumulation of nucleotides into the extracellular milieu. Clinical trials have shown the benefit of antagonists of the ADP platelet receptor(s) in the prevention of vascular accidents in patients with atherosclerosis. Therefore, we anticipate that a deeper understanding of the involvement of P2 receptors in atheroma formation will open new avenues for drug design and therapeutic intervention. British Journal of Pharmacology (2002) 135, 831,842; doi:10.1038/sj.bjp.0704524 [source]

Localization of matrix metalloproteinase 2 within the aneurysmal and normal aortic wall

BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 10 2000
M. Crowther
Background Current research has shed new light on the role of matrix metalloproteinase (MMP) 2 in the development of abdominal aortic aneurysms (AAAs). MMP-2 is a major protease in the wall of small aneurysms and is produced at increased levels by smooth muscle cells derived from AAAs compared with normal controls. In vivo, MMP-2 is produced as an inactive proenzyme that is activated predominantly by the cell membrane-bound enzyme, membrane type 1 matrix metalloproteinase (MT1-MMP). This study investigated the production of the MMP-2,MT1-MMP,tissue inhibitor of metalloproteinases (TIMP) 2 system within the wall of aortic aneurysms and in age-matched control arterial tissue. Methods Arterial tissue from four patients with aortic aneurysms and four age-matched aortic samples was examined for the production and expression of MMP-2, TIMP-2 and MT1-MMP protein using immunohistochemistry, in situ hybridization and in situ zymography. Results All components of the MMP-2,TIMP-2,MT1-MMP enzyme system were detected in the arterial wall of both aneurysm and control samples, specifically in the medial tissue. The enzymes co-localized with medial smooth muscle cells. Gelatinolytic activity was localized to elastin fibres in normal and aneurysmal aorta. Conclusion The presence of MT1-MMP within the media of arterial tissue suggests a powerful pathway for the activation of MMP-2. The localization of the MMP-2,TIMP-2,MT1-MMP enzyme system to the medial layer of the arterial wall gives support to the concept that this system may play an aetiological role in the pathogenesis of AAAs. © 2000 British Journal of Surgery Society Ltd [source]

Scanning electron microscopic analysis of different drug eluting stents after failed implantation: From nearly undamaged to major damaged polymers,

CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS, Issue 6 2010
Marcus Wiemer MD
Abstract Background: Implantation of drug eluting stents (DES) in tortuous and/or calcified vessels is much more demanding compared with implantation of bare metal stents (BMS) due to their larger diameters. It is unknown whether drug eluting stent coatings get damaged while crossing these lesions. Methods: In 42 patients (34 male, 68.1 ± 10 years) with 45 calcified lesions (15.9 mm ± 7.9 mm), DES could not be implanted, even after predilatation. Diabetes was present in 19 patients (45 %). Sixty-one stents were used; 19 Cypher selectÔ, 18 Taxus LibertéÔ, 10 CoStarÔ, 5 Endeavor RXÔ, 4 Xience VÔ. 3 Janus CarbostentÔ, 1 Yukon Choice SÔ, and 1 AxxionÔ DES. The entire accessible surface area of these stents, in either the unexpanded and expanded state, were examined with an environmental scanning electron microscope (XL30 ESEM, Philips) to evaluate polymer or surface damage. Results: The polymers of Taxus Liberte, Cypher Select, Xience V, CoStar, and Janus DES were only slightly damaged (less than 3% of surface area), whereas the Endeavor RX Stents showed up to 20% damaged surface area. In DES without a polymer (Yukon and Axxion), it could be shown that most of the stent surface (up to 40%) were without any layer of drug. Conclusion: Placement of drug eluting stents in tortuous vessels and/or calcified lesions could cause major surface damage by scratching and scraping of the polymer or drug by the arterial wall, even before implantation. There were remarkable differences among the stents examined, only minor damage with the Cypher, Taxus Costar, Janus, and Xience V, whereas the Endeavor, the Yukon, and the Janus DES showed large areas of surface injury. © 2009 Wiley-Liss, Inc. [source]

Cell growth and cholesterol metabolism in human glucose- 6-phosphate dehydrogenase deficient lymphomononuclear cells

CELL PROLIFERATION, Issue 3 2002
Batetta B.
Atherosclerosis is an inflammatory-fibroproliferative response of the arterial wall involving a complex set of interconnected events where cell proliferation (lymphomonocytes, and endothelial and smooth-muscle cells) and substantial perturbations of intracellular cholesterol metabolism are considered to be among the main features. Glucose-6-phosphate dehydrogenase (G6PD), the key enzyme of the hexose-monophosphate shunt pathway, is an essential enzyme involved in both cell growth and cholesterol metabolism, raising the question as to whether G6PD deficiency may have metabolic and growth implications in a deficient population. In the present study, we investigated cell growth and cholesterol metabolism in peripheral blood lymphomononuclear cells (PBMC) from G6PD-normal (n = 5) and -deficient (n = 5) subjects stimulated with lectins (phytohaemoagglutinin and Concanavalin A). G6PD activity, DNA ([3H]-thymidine incorporation) cholesterol synthesis and esterification ([14C]-acetate and [14C]-oleate incorporation), and G6PD, HMGCoA reductase and low density lipoprotein (LDL) receptor mRNA levels (RT-PCR) all increased following lectin stimulation in both normal and G6PD-deficient cells. However, these parameters were significantly lower in G6PD-deficient cells (P < 0.05). It is of interest that G6PD-deficient PBMC, which showed lower expression of G6PD and higher expression of the LDL receptor gene than normal PBMC under basal conditions, exhibited an opposite pattern after stimulation: G6PD and HMGCoA reductase being expressed at significantly higher levels in deficient than in normal cells (P < 0.05). We conclude that the reduced capability of G6PD-deficient cells to respond to mitogenic stimuli and to synthesize cholesterol esters may represent favourable conditions for reducing the risk of cardiovascular diseases. [source]