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)

Diabetes and aging are commonly accompanied by arterio- and atherosclerosis. Infiltration of the arterial subendothelial intima by macrophages/monocytes is an important early event preceding the development of atheromatous lesions; these macrophages are known to produce mitogenic factors in early atherosclerotic lesions. It has been previously shown that, over time, vascular matrix accumulates proteins nonenzymatically modified by advanced glycosylation end products (AGEs). In view of the fact that macrophages/monocytes have AGE-specific receptors associated with the expression of several growth factors, we investigated the possibility that AGEs mediate initial monocyte-vessel wall interactions that occur before overt formation of vascular lesions. This study demonstrates that (i) in vitro- and in vivo-formed AGEs are chemotactic for human blood monocytes, (ii) sub-endothelial AGEs can selectively induce monocyte migration across an intact endothelial cell monolayer, and (iii) subsequent monocyte interaction with AGE-containing matrix results in the expression of platelet-derived growth factor. These results support the existing hypothesis that in vivo-forming glucose-derived protein adducts can act as signals for the normal turnover of senescent tissue protein by means of the AGE-specific receptor system. Time-dependent glucose-induced deposition of AGEs on matrix proteins may promote monocyte infiltration into the subendothelium. Subsequent AGE-triggered macrophage activation and consequent elaboration of proliferative factors may normally coordinate remodeling but may also lead to the diverse pathogenic changes typical of arterio- and atherosclerosis in diabetic or aging populations.
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PMID:Advanced protein glycosylation induces transendothelial human monocyte chemotaxis and secretion of platelet-derived growth factor: role in vascular disease of diabetes and aging. 224 77

We have investigated the effect of interleukin-1 (IL-1) on the growth of vascular smooth muscle cells (VSMC) isolated from rat aortae. Murine recombinant IL-1 alpha increased tritiated leucine incorporation into VSMC. IL-1 also stimulated tritiated thymidine uptake by VSMC in a dose-dependent manner. On the other hand, Ca2(+)-channel blocker, verapamil, inhibited the IL-1-induced thymidine uptake by VSMC with an IC50 of 10(-8) M. Antibody specific for platelet-derived growth factor (PDGF) also totally inhibited the IL-1-induced thymidine uptake. IL-1 showed no effects on the intracellular Ca2+ level in VSMC. Above results support the premise that IL-1 promotes the growth of VSMC via induction of endogenous PDGF production and might thus participate in the abnormal proliferation of VSMC that occurs early in atherogenesis.
Atherosclerosis 1990 Oct
PMID:Mitogenic action of interleukin-1 alpha on vascular smooth muscle cells mediated by PDGF. 228 97

Migration of smooth muscle cells (SMC) in the arterial wall is important in the pathogenesis of atherosclerosis and is presumably regulated in both normal and atherosclerotic tissues. In this study, the effect of transforming growth factor-beta (TGF-beta) on the migration of rat aortic SMC was examined. TGF-beta alone enhanced the migration of SMC at concentrations of 10 to 50 pg/ml and its maximal effect was similar to that of platelet-derived growth factor (PDGF). Checker board analysis showed that TGF-beta had a chemotactic, but not a chemokinetic effect. PDGF also enhanced the migration in a dose-dependent manner and TGF-beta inhibited the PDGF-induced migration dose-dependently at 1.0 pg/ml to 1.0 ng/ml. These data suggest that TGF-beta is a bifunctional regulator of the migration of aortic SMC.
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PMID:Bifunctional effects of transforming growth factor-beta on migration of cultured rat aortic smooth muscle cells. 235 28

Vessel wall injury and lipid deposition in the walls of arteries can contribute to the development of atherosclerotic lesions. The mitogen (platelet-derived growth factor) for smooth muscle cells that is released from platelets that adhere to the sites of injury contributes to vessel wall thickening, as does the organization of mural thrombi. Although many arterial thrombi result from fissure or rupture of the fibrous cap of lipid-rich atherosclerotic plaques, thrombi that result from shear-induced platelet aggregation and disturbed blood flow at stenotic lesions also contribute to the thromboembolic clinical complications of atherosclerosis. Prevention of thrombus initiation requires a better understanding of platelet interaction with injured vessel walls and of the ways in which this process may be inhibited. A crucial factor in the management of thrombus formation in severely injured vessels is restoration of a normal pattern of blood flow. Theoretically, it may be possible to use angioplasty (to remove atherosclerotic lesions and to dilate stenosed vessels) and to use new therapeutic interventions (to prevent the accumulation of an initial layer of platelets on the acutely injured surface) to reduce the probability of restenosis and thrombosis at these sites.
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PMID:Platelets, blood flow, and the vessel wall. 240 65

The response-to-injury hypothesis of atherosclerosis describes how risk factors associated with atherogenesis may alter endothelial function, creating opportunities for endothelial cell separation and interactions with blood monocyte/macrophages and platelets that result in the intimal proliferative smooth-muscle lesions of atherosclerosis. Growth factors derived from platelets (platelet-derived growth factor) and macrophages (macrophage-derived growth factor) are described and their possible role in atherogenesis is presented. Possible approaches for the prevention of atherosclerosis include the development of means of interfering with the activity of these growth factors.
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PMID:Platelets, platelet-derived growth factor, growth control, and their interactions with the vascular wall. 240 93

The early state of atherosclerosis is characterized by a nodular proliferation of smooth muscle cells in the arterial intima. It has been suggested that this proliferation is initiated by platelet-derived growth factor (PDGF) released from aggregating platelets in connection with endothelial injury. In the present study platelet reactivity and mitogenic activity of plasma and serum were compared in young male survivors of myocardial infarction with angiographically demonstrable coronary atherosclerosis and in healthy subjects of similar age. Young post-infarction patients with coronary atherosclerosis had lower ED50 values of ADP-induced platelet aggregation. Furthermore plasma and serum from the patients contained increased amounts of mitogenic activity. Experiments using antibodies against platelet-derived growth factor indicated that the increase in mitogenic activity represented elevated concentrations of free PDGF growth factor in plasma. The results raise the possibility of a connection between increased levels of free PDGF and the proliferative reaction that characterizes early lesion progression.
Atherosclerosis 1986 Sep
PMID:Increased platelet-derived mitogenic activity in plasma of young patients with coronary atherosclerosis. 242 75

Arterial smooth muscle cell (SMC) proliferation is thought to be an essential aspect of the development of human atherosclerotic lesions. In this study we posed the question, could a growth factor gene be transcriptionally active in atherosclerotic tissue? We found that transcripts from the sis gene, which encodes one of the two chains of platelet-derived growth factor, were present in surgically removed human carotid artery lesions at levels 5-fold greater than the low level of constitutive expression detected in normal artery. This demonstrates that a growth factor could be synthesized endogenously within human atherosclerotic lesions. Although atherosclerotic lesions are composed predominantly of SMC, large numbers of infiltrating macrophages, T cells, and endothelial cells can also be present, raising the possibility that one of these secondary cell types, rather than SMC, could be responsible for the sis transcripts. Human macrophages activated in culture contained 2- to 4-fold more sis RNA, per micrograms of total cellular RNA, than lesions, whereas T cells activated in culture did not contain significant levels. Cultured human endothelial cells expressed sis transcripts at higher levels than macrophages. Since human arterial SMC in culture express receptors for and are mitogenically responsive to platelet-derived growth factor, transcription of the sis gene by cells within lesions, whether these cells are SMC themselves, macrophages, endothelial cells, or another cell type, suggests that an autocrine and/or paracrine proliferative mechanism is important in the pathogenesis of atherosclerosis.
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PMID:sis (platelet-derived growth factor B chain) gene transcript levels are elevated in human atherosclerotic lesions compared to normal artery. 243 49

Proliferation of smooth muscle cells (SMC) in the arterial intima of man and experimental animals is important in the pathogenesis of atherosclerosis. Vascular SMC proliferation in vitro is stimulated by a number of agents, including the potent protein mitogen, platelet-derived growth factor (PDGF). Recent studies on rat arterial SMC indicate that these cells may, under certain circumstances, synthesize PDGF protein mitogens, suggesting that the regulation of SMC proliferation in vivo may have an autocrine or paracrine component. In this study we demonstrate that cultured nonhuman primate (baboon) aortic SMC transcribe both the PDGF-A and PDGF-B genes but do not secrete detectable mitogenic activity characteristic of native PDGF. The absence of this activity was not due to the presence in the cell conditioned medium of factors inhibitory for PDGF-mediated mitogenic activity. Metabolic labeling of the cells and immunoprecipitation with specific antibodies to human PDGF did not detect a dimeric (30 kDa) PDGF protein in either the intracellular or extracellular compartments, but instead identified PDGF-related proteins of molecular weight 12 kDa and 100 kDa. These data suggest the presence in vascular SMC of a mechanism regulating the translation of PDGF mRNA that may play an important role in the control of SMC proliferation in vivo.
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PMID:Cultured primate aortic smooth muscle cells express both the PDGF-A and PDGF-B genes but do not secrete mitogenic activity or dimeric platelet-derived growth factor protein. 245 35

The authors have investigated the effects of cytokines and lipopolysaccharide (LPS) on mRNA levels of c-sis (platelet-derived growth factor (PDGF)-B chain), PDGF-A chain, and interleukin 1 beta (IL-1 beta) genes in human vascular endothelial cells (EC). IL-1, tumor necrosis factor (TNF), and LPS not only enhanced the accumulation of c-sis mRNA, but also induced IL-1 beta gene expression. Interferon-gamma (IFN-gamma), in contrast, suppressed the accumulation of c-sis mRNA profoundly and PDGF-A chain mRNA to a lesser extent. The cytokine, in addition, suppressed the release of PDGF-like proteins by EC, while maintaining the growth of EC. IFN-gamma, however, augmented the levels of IL-1 beta mRNA in cultured EC in association with LPS or IL-1, suggesting that the suppression of c-sis expression was not mediated through modulation of IL-1 gene expression by IFN-gamma. These results raise the possibility that IFN-gamma may play a novel regulatory role in the pathogenesis of vascular diseases such as atherosclerosis and vasculitis.
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PMID:Interferon-gamma modulates messenger RNA levels of c-sis (PDGF-B chain), PDGF-A chain, and IL-1 beta genes in human vascular endothelial cells. 249 3

Our previous studies have demonstrated that platelet-derived growth factor (PDGF) modulated cellular responses to interleukin-1 (IL-1). In this communication, we show that PDGF regulates expression of IL-1 receptor (IL-1 R) gene. Treatment of quiescent cultures of Balb/c 3T3 fibroblasts with PDGF produced 20-30-fold stimulation of IL-1 R mRNA with a concomitant increase in cell surface 125I-binding. IL-1 R mRNA accumulation occurred after an initial lag period and with a time course preceding the increase in 125I-IL-1 binding to cells. Induction of IL-1 R mRNA was blocked by inhibitors of protein synthesis, suggesting that a product of a gene expressed immediately after PDGF addition is required for IL-1 R gene expression. These latter data provide evidence for an ordered sequence of expression of PDGF-inducible "immediate early" gene(s) and IL-1 R gene. These results suggest that in connective tissues, PDGF may be an important determinant in initiating and maintaining cellular responses to IL-1. Such responses may have important consequences in the actions of IL-1 under normal and pathological conditions such as arthritis and atherosclerosis.
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PMID:Platelet-derived growth factor induces interleukin-1 receptor gene expression in Balb/c 3T3 fibroblasts. 253 9


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