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)

Proliferation of vascular smooth-muscle cells occurs during the development of atherosclerosis and the remodeling of arteries that accompanies chronic systemic or pulmonary hypertension. To help define the signals that initiate this abnormal growth, we cultured smooth-muscle cells from human atherosclerotic plaques. These cells (n = 9) released material into their culture medium that stimulated the proliferation of aortic smooth-muscle cells to a mean (+/- SD) level 5.1 +/- 1 times that in control medium. Part of this activity was due to molecules that resemble a mitogen first isolated from platelets and known as platelet-derived growth factor (PDGF), since these cells released PDGF measured in a radioreceptor assay (355 +/- 117 pg per milliliter per 48 hours; n = 6) and since anti-PDGF antibody neutralized 38 +/- 7 percent of this mitogenic activity (range, 13 to 60 percent; n = 6 carotid-plaque isolates). Two human genes encode distinct PDGF subunits that form dimers in different combinations to create biologically active PDGF. Cells cultured from human atheroma contained mRNAs for the PDGF A chain (16 of 17 isolates) but none (of 13) that encoded PDGF B chain (the c-sis proto-oncogene product). We conclude that smooth-muscle cells from diseased human arteries can secrete mitogenic activity, some of which resembles PDGF, and that these cells express the gene for the PDGF A chain selectively. This capacity to produce an endogenous, potentially self-stimulatory (autocrine) growth factor may help to explain how replication of smooth-muscle cells can begin, even while the endothelial barrier remains morphologically intact, early in atherogenesis.
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PMID:Production of platelet-derived growth factor-like mitogen by smooth-muscle cells from human atheroma. 336 60

Growth factors and their receptors may be involved in initiation and progression of atherosclerotic intima changes. In this study, sections of human arteries in different stages of atherosclerosis were investigated for cellular expression of PDGF B, PDGF beta receptors and IGF I receptors. The applied immunohistochemical approach detected IGF I receptor synthesis in endothelial cells of atherosclerotic vessels. A possible role in atherogenesis may be seen in the control of IGF I transfer into subendothelial tissues. PDGF B chain production was observed in endothelial cells and macrophages in all stages of lesion development. The corresponding receptor for PDGF B (PDGF beta receptor) was expressed by transformed smooth muscle cells within the thickened intima from the stage of macrophage infiltration onwards. These results support the thesis that locally produced PDGF acts as a mitogen on smooth muscle cells and may promote proliferation during atherogenesis.
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PMID:Immunohistochemical localization of PDGF B, PDGF beta receptors and IGF I receptors during atherogenesis. 782 84