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)

Cultured bovine aortic endothelial cells secrete a potent migration-stimulating factor for vascular smooth muscle cells (SMCs) and adventitial fibroblasts. Vascular pericytes are 20-fold less responsive, and endothelial cells themselves do not respond at all. Checkerboard analysis of SMC migration in a micro-chemotaxis chamber assay shows that the factor is chemotactic. Chemotactic activity for SMCs and adventitial fibroblasts is specifically inhibited by antibodies against platelet-derived growth factor. Endothelial cells cultured on nitrocellulose filters secrete the platelet-derived growth factor-like factor almost exclusively into the basal compartment. We suggest that this factor plays an important role in the recruitment of vascular wall cells during the morphogenesis of blood vessels and pathological conditions, such as atherosclerosis.
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PMID:Polarized secretion of a platelet-derived growth factor-like chemotactic factor by endothelial cells in vitro. 368 Mar 70

Current ideas about the mechanism of wound healing and the pathogenesis of atherosclerosis, pulmonary fibrosis and hepatic fibrosis suggest a central role for the mononuclear phagocyte in attracting and/or stimulating the proliferation of mesenchymal cells. We demonstrate here that activated human blood monocytes, but not resting monocytes, release a mediator that attracts smooth muscle cells and cooperates with other mediators to stimulate fibroblast proliferation. This mediator is very similar to platelet-derived growth factor (PDGF): its chromatographic properties and chemical stability are similar to those of PDGF, it competes with 125I-PDGF for binding to fibroblasts and it immunoprecipitates with anti-PDGF antibodies. In parallel, stimulated monocytes, but not resting monocytes, express the c-sis proto-oncogene, a gene coding for one of the PDGF chains, consistent with the concept that expression of the c-sis proto-oncogene may be involved in the ability of mononuclear phagocytes to modulate the accumulation of mesenchymal cells.
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PMID:Activated human monocytes express the c-sis proto-oncogene and release a mediator showing PDGF-like activity. 394 44

The effect of prostaglandins (PG) on initiation of DNA synthesis in arterial smooth muscle cells (SMC) stimulated with platelet-derived growth factor (PDGF) was examined. A concentration of 10 ng/ml PGE1 inhibited DNA synthesis, measured as autoradiographically labeled nuclei, by about 70%. Similar results were obtained with PGE2 and PGD2 but at concentrations 10-20 times higher, whereas PGF2 alpha lacked effect. The inhibitory action of the prostaglandins was restricted to the first 6 h of the lag phase. Treatment with PGE1 also raised the intracellular concentration of cyclic AMP, indicating that the inhibition may be mediated via changes in the levels of cyclic nucleotides.
Atherosclerosis 1984 Oct
PMID:Prostaglandin E1 inhibits DNA synthesis in arterial smooth muscle cells stimulated with platelet-derived growth factor. 609 30

Arteriolar wall thickness was measured in cigarette smokers by means of eyepiece micrometry, paper planimetry and computerized planimetry. Myocardial and renal arterioles in such smokers showed significant thickening of their walls. This thickening was mainly attributable to an increase in collagen and smooth muscle. The adventitia of small to medium-sized intramyocardial coronary arteries showed an increase in collagen. Platelets are known to be more adhesive to the vessel wall in smokers. It is suggested that platelet-derived growth factor, released in the vessel wall, may promote proliferation of connective tissues, thus leading to the vascular thickening described.
Atherosclerosis 1984 Aug
PMID:Myocardial and renal arteriolar thickening in cigarette smokers. 647 70

It has been proposed that a platelet-derived growth factor (PDGF) may play an important role in the genesis of atherosclerosis by promoting proliferation of smooth muscle cells. The present study shows evidence that fenofibric acid inhibits the growth promoting activity of PDGF on cultured smooth muscle cells. When smooth muscle cells are in a quiescent state by feeding them a PDGF -and lipoproteins- deficient medium, addition of a platelet extract induces DNA synthesis in a synchronous fashion. A 6 hours' exposure of cells to this extract is sufficient for this effect. Fenofibric acid could inhibit this synthesis when the compound was present in the culture medium concomitantly with platelet extract. This result suggests that fenofibric acid target is a cellular event attendant on PDGF-induced growth promotion. Fenofibric acid is a hypolipidemic drug which inhibits 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCoA reductase) activity, the limiting step of endogenous cholesterol synthesis. If any endogenous cholesterol is available, smooth muscle cell cholesterol needs for proliferation can be supplied by LDL-cholesterol. As the addition of LDL to the culture medium did not overcome fenofibric acid inhibition, this demonstrates a cholesterol independent mechanism for the anti-PDGF growth promoting activity. The fact that fenofibric acid, a hypolipidemic drug, can also inhibit growth promoting activity of PDGF suggests that this drug can be effective on the prevention of atherosclerosis and cardiovascular diseases by at least two independent mechanisms.
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PMID:Evidence for the inhibition of platelet-derived growth factor induced rat smooth muscle cells DNA synthesis by fenofibric acid at the Go/G1 cell cycle level. 688 56

Endothelial and smooth muscle cell proliferation has an important role in the pathogenesis of atherosclerosis. To study the effect of serum and some of its putative growth factors on DNA synthesis, the incorporation of thymidine into DNA was studied in cultured human umbilical endothelial and rat aortic smooth muscle cells. DNA synthesis in endothelial cells was progressively stimulated by increasing concentrations of human serum, maximum stimulation occurring with 20% serum. Foetal calf serum had a much lesser effect on DNA synthesis in endothelial cells. Smooth muscle cells responded equally to human and foetal calf serum. Exposure to serum prepared to exclude the platelet-derived growth factor resulted in reduced DNA synthesis in smooth muscle cells. However, endothelial cells increased DNA synthesis in platelet-poor serum. Serum from which lipid had been extracted stimulated DNA synthesis less well than whole serum in both endothelial and smooth muscle cells. Insulin stimulated DNA synthesis in smooth muscle cells but not in endothelial cells, while ethinylestradiol, estrone and estriol had no effect on DNA synthesis in either type of cell. Thus cultured endothelial and smooth muscle cells differ in their requirements for human serum and in their response to platelet factor and to insulin.
Atherosclerosis 1980 Dec
PMID:Control of DNA synthesis in cultured vascular endothelial and smooth muscle cells--response to serum, platelet-deficient serum, lipid-free serum, insulin and oestrogens. 700 24

Although polyamine (PA) levels are believed to increase in response to mitogenic stimuli in all cells during growth, their role in arterial smooth muscle cell (ASMC) proliferation, an essential step in atherogenesis, is unknown. To determine whether the arterial wall mitogen, platelet-derived growth factor (PDGF) influences PA metabolism when cell cycle traverse is initiated, we examined its effects on the transport of the PA precursor [3H]putrescine (PUT) in culture in bovine and human ASMC. PUT uptake was stimulated in a dose-response relationship by PDGF-containing human serum (2-10%), and abolished in 24 h without it. Inhibition of this uptake by spermidine and the lack of effect of thymidine, leucine and ornithine indicated that uptake was by a PA-specific mechanism. Without serum, platelet releasate containing PDGF stimulated PUT uptake but not that of leucine or glucose. While platelet-poor plasma alone also promoted PUT uptake, the combination of platelet releasate and platelet-poor plasma was required for maximal DNA synthesis. PUT uptake under these conditions reached a peak at 16 h, while the synthesis of DNA was maximal at 24 h. Supraphysiological concentrations of insulin, and fibroblast and epidermal growth factors, also stimulated the uptake of the labeled PUT both in the absence and presence of serum, but at much lower rates than those observed with platelet releasate. These findings indicate that the early replicative actions of a variety of mitogens for ASMC involve stimulation of PUT uptake and suggest that PA uptake must precede the initiation of DNA synthesis in ASMC during atherogenesis.
Atherosclerosis 1982 Jul
PMID:Polyamines and atherosclerosis. Platelet releasate and other mitogens stimulate putrescine transport in arterial smooth muscle cells. 705 98

Role of platelet-derived growth factor (PDGF) in myointimal thickening described in "response to injury" hypothesis was investigated with artery of rats in culture and with air-injured artery of rats. PDGF promoted cell growth in ring preparation of carotid artery in culture denuded with citrate. It did not promote any cell growth in preparations without denudation. Trapidil, a PDGF antagonist, inhibited the cell growth promoted by PDGF in the denuded arterial ring. Systemic injection of PDGF was performed for 8 days to rats with thrombocytopenia induced by injections of anti-platelet serum. This treatment caused myointimal thickening of carotid artery 10 days after denudation by means of air injury. Trapidil at oral intake levels of 1, 3 and 30 mg/kg/day inhibited this change observed in denuded site of artery. Trapidil at oral intake of 6 mg/kg/day also inhibited myointimal thickening observed 15 days after denudation of carotid artery by air injury in normotensive and spontaneous hypertensive rats both with normal platelet counts. These results evidenced the role of PDGF in myointimal thickening described in "response to injury" hypothesis and clinical use of trapidil may be a new approach to the treatment of atherosclerosis.
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PMID:Evidence for "response to injury" hypothesis. 715 55

Cultured mouse peritoneal macrophages secrete a growth-promoting activity that stimulates 3 types of nonlymphoid mesenchymal cells in vitro: fibroblasts, vascular smooth muscle, and vascular endothelium. Production of this macrophage-derived growth factor (MDGF) is directly related to the number of viable macrophages and their time in culture, and is independent of platelet- or plasma-derived serum growth factors. Treatment of cultured macrophages with latex, bacterial lipopolysaccharide, or phorbol myristate acetate results in increased growth factor activity. Preliminary biochemical characterization of MDGF indicates that it is a heat labile (100 degrees C, 2 min), non-dialyzable protein, which contains at least 1 essential disulfide bond. Growth-promoting activity is not adsorbed by CM-Sephadex chromatography, under conditions that effectively remove platelet-derived growth factor(s). Serine protease activity is not required for the action of MDGF. Secretion of macrophage-derived growth factor may be relevant to the function of mononuclear phagocytes in several pathologic processes, including the neovascularization and fibroplasia of wound healing, smooth muscle hyperplasia in atherosclerosis, and proliferative glomerulonephritis.
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PMID:Stimulation of nonlymphoid mesenchymal cell proliferation by a macrophage-derived growth factor. 720 74

Effects of dexamethasone, retinoic acid, prostaglandin E2 (PGE2), and Iloprost as a agonist of prostacyclin (A-PGI2) on DNA synthesis and production of a precursor of matrix metalloproteinase 1 (tissue procollagenase/proMMP-1) by human aortic smooth muscle cells were investigated. When after treatment with platelet-derived growth factor (PDGF), these agents were added to the cultures, DNA synthesis and production of proMMP-1 were inhibited in a dose-dependent manner. These results suggest that these agents are negative regulators of PDGF. Since these agents are present in the blood or produced in the blood wall, in addition, since PDGF plays the most important role in the process of atherosclerosis, we propose that these agents function in vivo as a systems of protection against atherosclerosis.
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PMID:Down-regulation in the production of matrix metalloproteinase 1 by human aortic intimal smooth muscle cells. 750 89


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