Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have no evidence of the precise derivation of myointimal cells, either in 'normal' intima or in atherosclerotic lesions. Neither has any derivation been eliminated. Efforts to establish the origin of the cells might be as helpful to our understanding of the lesions as have been the studies of proliferation of SMC, regardless of which one of the various theories of the pathogenesis of atherosclerosis we happen to support.
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PMID:Derivation of intimal smooth muscle cells in normal arteries and atherosclerotic plaques. An overview. 92 38

In order to clarify mechanisms determining different degrees of vulnerability of atherogenesis between the apical and the proximal lateral walls at branchings, both regions of the inferior mesenteric artery in human autopsy cases were investigated electron microscopically. The lateral wall and the apex have been accepted by many researchers as the most preferential and the most resistant sites, respectively, for the disease. In regard to blood flow, the apex is exposed to laminar high shear stress, but the outer lateral wall to turbulent low shear stress. In newborns, intimal thickness in the apex was greater than that in the lateral wall, due mainly to the proliferation of SMC. After the 3rd decade, collagen fibers drastically increased in the apical intima, and SMC embedded between the collagen fibers, modulating their phenotypes from synthetic to contractile. In the lateral intima, SMC remained as the synthetic type. Synthetic SMC are considered capable of proliferation in the arterial wall. The lateral intima was generally abundant in proteoglycans and lacked collagen (including subendothelial basement membranes) as well as elastic fibers, particularly in the upper part of the intima. Such a structural difference may cause favorable conditions for atherosclerosis. Results of in vitro studies revealed that collagen gel suppressed proliferation of SMC and changed their phenotype from synthetic to contractile. Therefore, laminar high shear stress gives the arterial wall resistancy to atherogenesis through this phenotypic change. Rabbits showed preferential regions in certain areas of the flow divider for lipid deposition which were different from those of human beings. These regions were covered by ellipsoidal endothelial cells, which should be exposed to relatively low mean shear stress. Ellipsoidal endothelial cells had already been observed in intact rabbits. Therefore, we can conclude that atherogenic processes could be initiated by relatively low mean shear stress in either humans or rabbits.
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PMID:The effects of augmented hemodynamic forces on the progression and topography of atherosclerotic plaques. 224 44

We have investigated the effects of insulin on the synthesis of prostacyclin and cell proliferation in cultured vascular smooth muscle cells, which have been thought to play important roles in the development of atherosclerosis. Prostacyclin was measured as 6-keto-PGF1 alpha in the culture medium, and cell proliferation as incorporation of [3H]thymidine into DNA. Our studies showed that insulin reduced production of prostacyclin and stimulated cell proliferation in SMC. Like insulin, dibutyryl cAMP inhibited the production of prostacyclin, whereas it did not stimulate cell proliferation. No significant changes in cAMP levels were found on the addition of insulin into the culture medium. Therefore, cAMP does not appear to be involved in the mechanisms of these insulin effects. These results again suggest that hyperinsulinemia could be one of the important factors in atherosclerosis.
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PMID:Effect of insulin on the production of prostacyclin and cell proliferation in cultured smooth muscle cells. 247 30

The capacity of vascular tissue in generating PGI2 has been accepted to be a key property in hemostatic balancing at a local level. Earlier it has been shown that PDGF is able to enhance SMC-proliferation. As this process is associated with c-AMP changes which again are influenced by PGI2, the question arose, whether PDGF itself exerts an effect on PGI2-synthesis. Using normal and atherosclerotic human arterial tissue, animal arteries and cultured cells with and without addition of various PDGF-concentrations this question was answered by means of bioassay and RIA-determination in a static and a pulsatile perfusion chamber system as well. In general, between 10 and 50 ng PDGF/ml, a significant increase either in PGI2-formation or 6-oxo-PGF1 alpha can be seen. A similar dose dependent stimulation of PGI2-synthesis can be monitored for vascular tissue and cultured cells as well. Static incubation and perfusion chamber experiments reveal comparable findings of PDGF stimulatory capacity on PGI2-formation. In contrast, no such effect can be seen using human umbilical artery. The half-life of PGI2-formation in the perfusion chamber model is comparable in presence and absence of PDGF as well. The stimulatory effect of PDGF on atherosclerotic vascular tissue is significantly less pronounced than onto normal one. Concluding from our findings we speculate that PGI2 prevents PDGF-release from platelets, thus decreasing smooth muscle cell proliferation and improving cellular lipid metabolism; an insufficient response of vascular tissue onto PDGF to generate PGI2 might be a key event in the pathogenesis of early atherosclerosis favouring a negative vicious cycle.
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PMID:Stimulation of prostacyclin formation by the platelet-derived growth factor--an important pathomechanism for atherogenesis? 305 97

We investigated two monoclonal antibodies (MAbs) which recognize rabbit atherosclerotic tissues. In particular, one antibody, 2P1A2, is specific for rabbit aortic smooth muscle cells (RASMCs). We used RASMCs in primary culture to produce and screen MAbs directed towards the cell surface. The specificity of the described antibodies was tested on a battery of tissue cryosections of different origin (rabbit, rat and human) by immunological staining. 2P1A2 shows an exclusive immunolabeling for SMCs present inside rabbit atherosclerotic plaque. This MAb shows inside the fibrous plaque a staining similar to two other SMC-specific antibodies (anti-desmin and anti-alpha-actin). In an early stage of atherosclerosis, close to the internal elastic lamina, underlying a fibrous plaque, 2P1A2 detects some SMCs; in contrast, anti-desmin and anti-alpha-actin fail to stain such SMCs. This antibody may be therefore considered as directed specifically against SMCs in an activated state. The other antibody which we describe, 1PC1, stains a pericellular antigen expressed by cultured SMCs and shows a specificity for smooth muscle tissues. 1PC1 MAb strongly stains the fibrous plaque of atherosclerotic rabbit aorta and the recognized epitope is present inside the aortic media. These two antibodies may be useful in the recognition of vascular SMCs during the atherosclerotic process.
Atherosclerosis 1988 Nov
PMID:Detection of atherosclerotic plaque with two monoclonal antibodies. 2P1A2 monoclonal antibody is specific for smooth muscle cells in atherosclerotic plaque. 306 71

Subendothelial cells (SEC) were obtained from the inner intimal layer of adult human aorta by collagenase treatment. SEC were identified in primary culture either as smooth muscle cells by staining with FITC-labeled antisera against human smooth muscle myosin or as macrophages, foam cells and contaminating endothelial cells by their uptake of malondialdehyde treated low density lipoproteins labeled with fluorescent dye 3,3'-dioctadecylindocarbocyanine. Between 1 and 5 days in culture, along with smooth muscle cells (SMC, 38-82%), endothelial cells (0-9%), macrophages and foam cells (2-32%), one more type of cell was found. This cell type resembled SMC in size and shape, but was not stained by antisera to SMC myosin. By ultrastructural criteria these cells were characterized as modulated SMC for they contained prominent rough endoplastic reticulum and Golgi complex together with basement membrane and a large number of plasmalemmal vesicles. Like SMC they reacted with phalloidin and were stained by anti-vimentin but not by anti-desmin monoclonal antibodies. The proportion of such cells varied from 5 to 33% of total cell number and increased in parallel to macrophages and foam cells in vessels with well developed atherosclerotic lesions. We conclude that the applied technique may be used for identification of cultured vascular cells including modulated SMC.
Atherosclerosis 1988 May
PMID:Identification of intimal subendothelial cells from human aorta in primary culture. 313 80

The focal entry and accumulation of LDL within the arterial wall of the normal animal may represent an early stage in the development of the atherosclerotic plaque. Concentrations of LDL 10 to 100 times normal medial concentrations might be difficult to clear from the arterial wall, permitting accumulation of lipid. Elevated LDL concentrations, in proximity to smooth muscle cells, appear to stimulate SMC proliferation. High LDL concentrations might also enhance mononuclear cell adhesion to endothelium. Since LDL has a high affinity for heparin and heparin for growth factors, LDL accumulation may be a mechanism for the concentration of such materials in the intima. The observation of markedly enhanced macromolecular permeability foci could be related to several potential mechanisms of initiation of atherosclerosis. This observation is of particular note when the focal occurrence of atherosclerosis is considered. Although atherosclerosis is seen as a generalized thickening of the intima, it is the focal narrowing of the lumen that is often responsible for the stenosis which produces symptoms such as angina or myocardial infarction.
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PMID:Endothelial cell perturbation and low-density lipoprotein. Quantitative autoradiography. 343 38

Bovine arterial smooth muscle cells in culture were incubated in hypoxia and total cellular DNA and collagen secretion during and after the hypoxic period was measured as well as the effect of conditioned medium from hypoxic cells on these parameters. Collagen secretion decreased by 16.4% compared to controls during hypoxia but was increased by 41.4% in the post-hypoxic period. Total cellular DNA was significantly lower after both periods. New cultures, receiving conditioned medium from hypoxic cultures, showed an increased collagen secretion by 32.2% compared to controls while total cellular DNA was not changed. Growth stimulating activity, previously shown to be released from lysed cultured SMC, was assayed by exposing SMC cultures to supernatant from lysed cells that had been incubated in hypoxia or exposed to other potential atherogenic stimuli. The growth stimulating activity per cell could be increased by incubating cells in hypoxia, or exposing them to low density lipoproteins or cigarette smoke condensate in concentrations high enough to cause a decrease in cell number. It was suggested that the described effects might contribute to increased cell proliferation and collagen formation in the development of atherosclerosis.
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PMID:Effects of hypoxia and other injurious stimuli on collagen secretion and intracellular growth stimulating activity of bovine aortic smooth muscle cells in culture. 361 68

The capacity of arterial SMCs to produce PGI2 when stimulated by exogenous AA was studied in proliferative and confluent cultured cells and at different periods following endothelial denudation in vivo. PGI2 production per cell was doubled during the exponential growth-phase in culture. By contrast, increased PGI2 formation did not correlate with mitotic activity in intimal regeneration tissue but with the presence of SMCs in a synthetic phenotype. The present results suggest a potential role for PGI2 in SMC differentiation and proliferation.
Atherosclerosis 1984 Jan
PMID:Prostacyclin synthesis by proliferative aortic smooth muscle cells. A kinetic in vivo and in vitro study. 632 Aug 41

Excessive growth of the arterial smooth muscle is essential for the development of atherosclerosis and leads to arterial insufficiency in several other conditions. It is therefore important to elucidate the mechanisms that regulate the growth of the human arterial smooth-muscle cell, SMC. Like other untransformed cells, SMC require plasma for sustained growth in vitro. As found in an earlier study most of the material in plasma which stimulates SMC growth is related to the lipoproteins (LP), and is widespread among LP of different density classes. In the present study we investigated whether the growth-stimulating activity might be more specifically related to certain lipoproteins defined by criteria other than density or particle size. Activity was assayed using human SMC and human lung fibroblasts as both a change of culture size and DNA synthesis. The growth-stimulating activity was confined to apo B-containing LP, as defined by their strong affinity to heparin-Sepharose, electrophoretic beta-mobility, the presence of apo B and the absolute requirement of low density lipoprotein (LDL) receptors for the growth-stimulating effect to appear. It was strongly potentiated by PDGF-BB. A much higher level of LDL was required to initiate synthesis of DNA in SMC than in fibroblasts but at optimal LDL concentration the degree of activation was similar for both cell types. Apo B-containing LP are very powerfully related to atherosclerosis. As intimal thickening is a primary change in atherogenesis, the growth-stimulating effect of them may be of direct pathogenetic importance.
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PMID:Growth-stimulating effect of lipoproteins on human arterial smooth-muscle cells and lung fibroblasts is due to apo B-containing lipoproteins, type LDL and VLDL, and requires LDL receptors. 766 14


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