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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A method is presented for growing large numbers of pure isolated smooth muscle cells from adult human, monkey, and rabbit blood vessels in primary culture. In the first few days in culture these cells closely resembled those in vivo and could be induced to contract with angiotensin II, noradrenaline and mechanical stimulation. They stained intensely with antibodies against smooth muscle actin and myosin. Fibroblasts and endothelial cells did not stain with these antibodies thereby allowing the purity of each batch of cultures to be monitored. This was consistently found to be better than 99%. The smooth muscle cells modified or "dedifferentiated" after about 9 days in culture to morphologically resemble fibroblasts. At this stage cells could no longer be induced to contract and did not stain with the myosin antibodies. Intense proliferation of these cells soon resulted in a confluent monolayer being formed at which stage some differentiated characteristics returned. The modification of "dedifferentiation" process could be inhibited by the presence of a feeder layer of fibroblasts or endothelial cells, or the addition of cAMP to the culture medium. Smooth muscle cells which had migrated from explants in primary culture, and cells in subculture, had morphological and functional properties of "dedifferentiated" cells at all times. The advantages of differentiated rather than "dedifferentiated" smooth muscle cells in culture for the study of mitogenic agents in atherosclerosis is discussed.
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PMID:Comparison of vascular smooth muscle cells from adult human, monkey and rabbit in primary culture and in subculture. 40 16

Proliferative activity of smooth muscle cells and foam cells characterizes experimental atherosclerotic plaques as they first appear. Immunohistochemical and ultrastructural methods were applied to cells arrested in metaphase by colchicine and the phenotype of cells in mitosis was detected. Most of the metaphase arrested FC found in aortic plaques of cholesterol fed New Zealand rabbits were positive to the anti-macrophage monoclonal antibody and negative to the anti-smooth muscle actin monoclonal antibody. Moreover, most of the metaphase blocked FC had the ultrastructural features of macrophages. These preliminary results further strengthen previous observations on rabbit plaques that the FC pool is mainly constituted by macrophages and show, for the first time, that the dimension of this pool depends not only on migration of circulating monocytes but also on the in situ proliferation of macrophages.
Atherosclerosis 1991 May
PMID:Foam cells of the rabbit atherosclerotic plaque arrested in metaphase by colchicine show a macrophage phenotype. 187 13

Vascular smooth muscle cells (VSMCs) are involved in a number of vascular disease processes including hypertension and atherosclerosis. However, their role in the pathogenesis of vascular disease is largely undetermined. We and others have studied rat VSMCs in cell culture as a model for VSMC behaviour in vivo. In recent experiments we have applied molecular biological techniques to compare genes expressed by normal contractile VSMCs with those expressed by VSMCs which have undergone several passages in cell culture. Using differential screening of a cDNA library derived from cultured rat aortic VSMC RNA we identified seven genes which are preferentially expressed by contractile VSMCs; alpha-smooth muscle actin, gamma-smooth muscle actin, calponin, phospholamban, tropoelastin, SM22 alpha and CHIP28, and two which are preferentially expressed in passaged cells which have down-regulated their contractile proteins; osteopontin (OP) and matrix Gla protein (MGP). In situ hybridization studies have confirmed that calponin and SM22 alpha, are highly expressed by medial VSMCs in human coronary arteries with little or no expression in the atheromatous intima whilst the converse is true for OP and MGP. Studies by ourselves and others have confirmed that OP is a marker for proliferating rat VSMCs both in vitro and in vivo. However, the evidence that OP is expressed by proliferating human VSMCs is less convincing.
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PMID:Gene expression and vascular smooth muscle cell phenotype. 758 79

To determine the extent and origin of the stimulation of 15-lipoxygenase activity in atherosclerotic aortas, formation of hydroxy-derivatives from arachidonic acid was measured by HPLC-analysis and 15-lipoxygenase mRNA expression was investigated by RNA blot and in situ hybridization in atherosclerotic and normal rabbit aortic tissues. The synthesis of hydroxy-eicosatetraenoic acids (HETE) from exogenously added [14C]arachidonic acid was unchanged in atherosclerotic aortas in comparison with healthy aortas, but pretreatment with indomethacin demonstrated that 15-HETE production resulted essentially (75%) from cyclooxygenase activity in healthy aorta and from lipoxygenase activity in atherosclerotic aorta. The RNA blot and in situ hybridization with radiolabelled oligonucleotide probe demonstrated that 15-lipoxygenase mRNA was strictly localized in intimal thickening of atherosclerotic aortas. The immunostaining using anti-alpha smooth muscle actin, revealed that smooth muscle cell rich areas of the intimal thickening expressed 15-lipoxygenase mRNA. In addition, RNA blot hybridization indicated that cultured smooth muscle cells from atherosclerotic aortas expressed strongly 15-lipoxygenase mRNA. These results demonstrate that augmentation of 15-lipoxygenase activity in atherosclerotic aortas is correlated with 15-lipoxygenase mRNA expression in atherosclerotic plaque, and that intimal smooth muscle cells were involved, in addition to macrophages, in the expression of 15-lipoxygenase.
Atherosclerosis 1995 Mar
PMID:15-Lipoxygenase expression in smooth muscle cells from atherosclerotic rabbit aortas. 760 58

In order to investigate the role of monocyte/macrophages and their relationship to the expression of macrophage colony-stimulating factor (MCSF) in pulmonary atherosclerosis, lungs were excised from rabbits that had been fed for 60 and 90 days on a diet containing 0.5% cholesterol. In the lungs, fatty streaks and elevated foam cell lesions predominated in the large or medium-sized elastic pulmonary arteries, while massive accumulation of foam cells in the intima of muscular arteries produced marked luminal narrowing and nearly complete occlusion. In these lesions, most of the foam cells were reactive with RbM2, a monoclonal antibody (mAb) against rabbit macrophages, while smooth muscle cell-derived foam cells were detected by mAb against smooth muscle actin in the deeper area of elevated foam cell lesions of elastic arteries. Ultrastructural observation confirmed the presence of monocytes in the intima, their differentiation into macrophages, and their transformation into foam cells in the atherosclerotic lesions. Immunohistochemical expression of MCSF was demonstrated in the endothelial cells, smooth muscle cells and foam cells. A minor macrophage-derived foam cell population was demonstrated to possess a proliferative capacity. These data suggest that MCSF is involved in the differentiation of monocytes into macrophages, their transformation into foam cells, and their proliferation during pulmonary atherogenesis.
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PMID:Immunohistochemical detection of macrophage-derived foam cells and macrophage colony-stimulating factor in pulmonary atherogenesis of cholesterol-fed rabbits. 778 88

The platelet derived growth factor (PDGF) plays an important role for development of atherosclerosis. We therefore immunostained carotid atheroma specimens for PDGF. We also detected dividing cell species of the atheroma with in vitro labeling of bromodeoxyuridine (BUdR). Thirty specimens of carotid atheroma were obtained by endarterectomy and they were incubated for 3 hours with Dulbecco's modified Eagle medium/20% fetal calf serum culture medium containing BUdR/fluorodeoxyuridine (FUdR). They were ethanol-fixed, thin-sliced, and immunostained for BUdR, PDGF, smooth muscle actin and macrophage. The PDGF immunoreactivity was mainly detected in the macrophages of the subendothelial area, where BUdR-positive cells were present. Percentage of BUdR-positive cells in the atheroma specimens ranged from 3% to 15%. The BUdR-labeled small cells were mainly located in the subendothelial area, and they were identified as non-foamy macrophages by double immunostaining with anti-macrophage antibody. The results indicate that nonfoamy macrophages have potentials for cell division and they might play an important role for the development and growth of atheroma by secreting PDGF.
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PMID:Expression of PDGF in relation to cell division in atherosclerotic intima of human carotid arteries. 858 24

The in vivo activity of depolymerized holothurian glycosaminoglycan (DHG), a newly developed polysaccharide anticoagulant, on neointimal formation induced by a balloon catheter in the left common carotid artery of rats was investigated. In every Sprague-Dawley rat weighing approximately 400 g, a Forgaty 2Fr balloon catheter was inserted from the left femoral artery to the left common carotid artery, and was passed through three times in order to denude the endothelium of the artery. These rats were divided into four groups by the following treatment protocols; DHG was given to rats by daily subcutaneous injection into their abdomens at a dose of 3 mg/kg or 10 mg/kg (D3 or D10 group). For controls, 250 microl saline was injected daily (C group). Furthermore, 1 mg/kg of unfractionated heparin was also injected daily as a comparison to DHG (H group). Each treatment was performed in six rats, and the injections were continued for two weeks after the catheterization. The area ratio of thickened intima/media (I/M ratio) treated with DHG decreased in a dose-dependent manner compared to the control. In addition, the ratio in the D10 group was significantly lower than in the control (P < 0.01). However, the ratio in the H group did not decrease. By anti-a smooth muscle actin antibody staining the intimal thickening layers were seen to be completely occupied by proliferated smooth muscle cells, and their amount in these layers was attenuated by the DHG treatment. This indicated that DHG has an inhibitory effect on intimal thickening induced by balloon catheterization, and that this might be due to the inactivation of aberrant smooth muscle cells by this agent.
Atherosclerosis 1997 Feb 28
PMID:Depolymerized holothurian glycosaminoglycan (DHG) prevents neointimal formation in balloon-injured rat carotid artery. 906 13

Immune/inflammatory responses of arterial vessel wall constituents to lipid metabolic disturbances have been postulated to contribute to the pathogenesis of atherosclerosis. Mycophenolate mofetil (MMF), an antiproliferative agent used in clinical transplantation, has been shown to inhibit smooth muscle cell (SMC) proliferation and decrease the recruitment of monocytes into sites of chronic inflammation. This study was conducted to determine the effect of MMF on atherosclerotic plaque development after cholesterol-induced injury. New Zealand white rabbits were fed a high-cholesterol diet containing 0.5% cholesterol and 8% peanut oil. The experimental group (n = 10) was given MMF (80 mg/kg/day subcutaneously); the control group (n = 10) received placebo injections. The aortas were harvested at 12 weeks for immunohistochemical analyses. SMCs were identified by reactivity with a monoclonal antibody (mAb) to alpha smooth muscle actin. Monocytes/macrophages were detected with mAb RAM 11. Cross-sectional areas of the media and neointima were measured using computer-assisted image analysis. The density of SMCs and macrophage/foam cells within the neointima was calculated by dividing the number of cells by the area of the plaque. Total cholesterol, triglyceride, high density lipoprotein, and low density lipoprotein were significantly increased compared with levels before the initiation of a high-cholesterol diet, but there were no significant differences between the MMF-treated and untreated groups. Neointimal area in aortic tissue sections of the MMF-treated group (0.586 +/- 0.602 mm(2)) was significantly lower when compared with that in control animals (1.082 +/- 0.621 mm(2)) (P < 0.05). The densities of neointimal SMCs and monocytes/macrophages in the control group were 778 +/- 293 and 341 +/- 90 cells/mm(2), respectively. MMF treatment significantly reduced the number of neointimal SMCs (506 +/- 185 cells/mm(2)) (P < 0.05). The number of monocytes/macrophages was also reduced after MMF treatment (260 +/- 124 cells/mm(2)) but not significantly. Our results demonstrate that the administration of MMF significantly reduced neointimal SMC accumulation and plaque development in a hypercholesterolemic model of atherosclerosis.
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PMID:Mycophenolate mofetil treatment reduces atherosclerosis in the cholesterol-fed rabbit. 1083 60

To evaluate the effect of hypercholesterolemia on apoptosis and proliferation after vascular injury, iliac arteries of hypercholesterolemic (HC) and normocholesterolemic (NC) rabbits were examined after balloon injury using TUNEL, immunohistochemical staining of PCNA, macrophages, smooth muscle actin and p53. In media, apoptosis occurred massively early after injury and then decreased. HC did not affect this early post-injury apoptosis but significantly increased apoptosis 14 days later (D14). Immediate apoptosis in media was followed by active proliferation. HC sustained a high activity of proliferation until D14. The changes of immunoreactivity to p53 over the same 14 day period parallel that of apoptosis. In intima, where cells were scarce initially, proliferative activity reached a peak at D7 and then decreased. HC significantly enhanced proliferation at D14. In intima proliferation was accompanied by a later low-level apoptosis. HC significantly enhanced this low-level apoptosis at D14. These effects of HC resulted in significantly increased areas of intima and media. The fundamental difference between HC and NC was the infiltration of macrophages in HC. In conclusion, balloon injury induces early massive p53-associated apoptosis followed by proliferation in media, whereas in intima, it induces active proliferation followed by a low-level apoptosis. Hypercholesterolemia does not affect the early post-injury apoptosis but enhances proliferation and low-level apoptosis at a later stage, which in turn results in intimal and medial hyperplasia.
Atherosclerosis 2000 Jun
PMID:Effect of hypercholesterolemia on the sequential changes of apoptosis and proliferation after balloon injury to rabbit iliac artery. 1085 23

Cholesteryl ester transfer protein (CETP) has been considered to mediate the transfer of cholesteryl ester from arterial wall, however, the distribution and production of CETP in human arterial wall remains unclear. Present study histopathologically demonstrated the distribution of CETP and CETP mRNA in the human aortic wall by immunohistochemistry and in situ hybridization. While CETP was constantly distributed in the media, the protein was recognized within the intima with fibrocellular thickening and atherosclerotic intima. Double immunostaining methods demonstrated CETP expression in smooth muscle cells in the intima and media. CETP mRNA was detected not only in intimal cells but medial smooth muscle cells. Intimal cells expressing CETP mRNA were considered to be monocyte-derived macrophages and smooth muscle cells by immunohistochemistries using two antibodies against smooth muscle actin and human macrophage on the subserial sections. Our in vivo study provides that CETP is produced by smooth muscle cells in the intima and media of human aorta, and it is suggested that arterial smooth muscle cells positively participate in the removal of excessive cholesteryl ester from the arterial wall by CETP production.
Atherosclerosis 2001 May
PMID:The distribution and production of cholesteryl ester transfer protein in the human aortic wall. 1136 94


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