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

Much has been learned in the past two decades about the impact of omega-3 fatty acids on human biology. These distinctive fatty acids are derived principally from marine sources such as fish and fish oil. They are rapidly incorporated into cell membranes after their ingestion in the diet and subsequently may alter a myriad of cellular functions. For example, eicosapentaenoic acid and docosahexaenoic acid may inhibit the synthesis of several prostaglandins and leukotrienes, as well as reduce the cellular production of cytokines or growth factors such as interleukin-1 or platelet-derived growth factor. Some of these functional changes found after fish-oil ingestion may have therapeutic implications in the treatment of human disease. Studies are now underway to investigate the effect of fish-oil preparations or more-purified omega-3 fatty acids on arterial injury, thrombosis or atherosclerosis, as well as to study their effects in certain inflammatory or cutaneous disorders, such as psoriasis. This paper will review the current body of research on marine oils and will focus specifically on the effects of omega-3 fatty acids in vascular biology and associated disease states. The potential toxicity of these fatty acids will be discussed, as well as current indications (or lack of them) for their therapeutic use in humans.
 ...
PMID:The vascular effects of omega-3 fatty acids. 266 16

The effect of endothelin (ET), a novel endothelium-derived vasoconstrictive peptide, on DNA synthesis was studied in cultured rat vascular smooth muscle cells (VSMC). ET stimulated incorporation of [3H]thymidine into DNA of the quiescent VSMC in a dose-dependent manner; the approximate half-maximal and maximal stimulation for DNA synthesis was induced with 2 x 10(-10) M and 10(-9) M, respectively. The stimulatory effect by ET on DNA synthesis was completely inhibited by the calcium channel blocker nifedipine. ET combined with epidermal growth factor and transforming growth factor-alpha, but not with platelet-derived growth factor, had synergistic effects. These data indicate that ET is a potent mitogen as well as a constrictor for VSMC, suggesting its potential role in the development of vascular disease.
Atherosclerosis 1989 Aug
PMID:Endothelin is a potent mitogen for rat vascular smooth muscle cells. 267 59

Accumulating mainly experimental evidence from research of the last 3 decades shows that many types of arterial wall injury can accelerate and intensify the development of atherosclerosis in arteries exposed to chronic hyperlipemia by increasing the permeability of their endothelium for plasma lipoproteins, proteins and several types of smooth muscle mitogens (including soluble platelet-derived growth factor). Of the numerous artery-injuring agents studied experimentally today only those that can be proven to operate in humans at concentrations and durations of action that injure animal arteries can be accepted as capable of playing a role in human atherogenesis. Seven such groups of agents can be recognized at present: blood turbulence, hypertension, certain viruses, metabolic disturbances (including hyperlipemia), certain immune insults, exogenous chemicals, and obstruction of adventitial lymphatics. Most of the above agents cause various degenerative changes in individual endothelial cells or open interendothelial junctions, and they seem to promote the penetration of plasma macromolecules into the wall in 3 different ways: directly through the altered endothelial cytoplasm, through opened interendothelial junctions or through transport in the cytoplasm of immigrating monocytes. None of the commonly occurring injury agents produce complete endothelial denudation of wide areas of the arterial cylinders. New findings from the transmission electron microscopic study of step-serial sections of human arteries obtained under conditions minimizing artificial endothelial loss indicate that endothelial denudation accompanied by platelet adherence and aggregation does not occur over early myoproliferative lesions but occasionally develops over small areas of advanced plaques with mostly necrotic or damaged caps and is, therefore, not an initiating event but a late complication of atherosclerosis. Light microscopic serial section studies of human thrombosed vessels in several centers reveal that thrombogenesis in most human atherosclerotic arteries is initiated by a severe structural injury of the cap of advanced plaques that leads to a microscopic break of the plaque surface through which some blood can enter the plaque interior before it is sealed by a thrombus.
 ...
PMID:The role of arterial wall injury in atherogenesis and arterial thrombogenesis. 268 99

Blood platelets are a rich source of growth factors, including platelet-derived growth factor, platelet-derived endothelial cell growth factor, and transforming growth factor beta. Platelet-derived growth factor stimulates the growth of mesenchymal cells such as fibroblasts and vascular smooth muscle cells, whereas platelet-derived endothelial cell growth factor is a mitogen for vascular endothelial cells. Transforming growth factor beta is a bifunctional regulator of cellular growth, but acts as a potent inhibitor for most cell types. Most of the growth regulatory substances in platelets have been reported to reside in platelet alpha-granules, but platelet-derived endothelial cell growth factor appears to be present in platelet cytoplasm. These growth factors may act at sites of injury as wound hormones. Moreover, they play important roles for some pathological conditions such as atherosclerosis, myelofibrosis, connective tissue diseases, and neoplastic disorders.
 ...
PMID:Platelet-derived growth factors. 269 47

During hemodialysis on cuprophane membranes, platelets are activated and release in plasma alpha-granule-specific substances such as PF4 or platelet-derived growth factor (PDGF). PDGF is the main source of mitogenic activity found in serum. In vitro, it induces the proliferation of smooth muscle cells (SMC) which is known to be involved in the development of atherosclerotic lesions. Atherosclerosis is one of the major complications of uremic patients undergoing chronic hemodialysis. To investigate whether this complication could be due to the dialysis itself, we measured the mitogenic activity in plasma of 10 patients undergoing hemodialysis on cuprophane membrane, using human arterial SMC in culture. Mitogenic activity in plasma increased about 3-fold during dialysis. These results may provide an argument in favor of a contribution of platelet activation and release of mitogenic activity to atherosclerosis in patients dialysed with cuprophane membranes.
 ...
PMID:Mitogenic activity on human arterial smooth muscle cells is increased in the plasma of patients undergoing hemodialysis with cuprophane membranes. 281 69

The chemotactic activities of inflammatory cell products for rat aortic smooth muscle cells (SMC) were examined in modified Boyden chambers. A checker board analysis revealed that interleukin-1 (IL-1), leukotriene B4 (LTB4), platelet-derived growth factor (PDGF) and inflammatory exudate from zymosan-activated air pouches stimulated chemotaxis of SMC. The chemotaxis, irrespective of the attractants used, was strongly inhibited by nilvadipine, a potent calcium antagonist, and the IC50 values were around 1 x 10(-10) M. Removal of extracellular calcium abolished the chemotactic activities of the attractants. These results suggest that inflammatory cells such as macrophages and polymorphonuclear leukocytes (PMN) have an important role in the migration of SMC into the intima during atherogenesis, and that nilvadipine might be useful for preventing and treating atherosclerosis.
Atherosclerosis 1988 Aug
PMID:Smooth muscle cell migration induced by inflammatory cell products and its inhibition by a potent calcium antagonist, nilvadipine. 285 Aug 8

Expression of B-type receptors for platelet-derived growth factor (PDGF) in frozen sections of blood vessels from tissues affected by abnormal vascular cell proliferation was investigated by immunohistochemical techniques and compared with expression of these receptors in blood vessels of normal tissues. Receptors were not expressed, or expressed at low levels, in vessels of normal tissues. In contrast, a pronounced expression of PDGF B-type receptors was seen on vascular smooth muscle cells in atherosclerotic plaques, rejected kidneys, and chronic synovitis. These observations suggest induction of PDGF B-type receptors on vascular smooth muscle cells in inflamed tissues, which would render such cells responsive to growth stimulation by PDGF released from captured platelets, or produced locally (eg, by inflammatory cells or smooth muscle cells). Autocrine or paracrine stimulation of cell growth caused by the effect of PDGF on cells with induced receptors may be important in the formation of the proliferative lesions found in atherosclerosis and in certain forms of chronic inflammation.
 ...
PMID:Induction of B-type receptors for platelet-derived growth factor in vascular inflammation: possible implications for development of vascular proliferative lesions. 289 41

The authors have previously shown that serum from young women receiving the same combined mestranol-norethindrone containing oral contraceptive (OC) preparation accelerated the proliferation of arterial smooth muscle cells (SMC) in tissue culture, and this in vitro effect was not a direct action of either of its estrongenic or progestagenic constituents. To identify the substance(s) which might contribute to this potentially atherogenic action, blood was obtained from 20 OC users, 18-25 years, and control women for the measurment of growth hormone, insulin, somatomedins (insulin-like growth factor IGF-I AND IGF-II), and the platelet alpha-granule constituents platelet-derived growth factor (PDGF), Beta-thromboglobulin, and platelet factor 4 (PF4). No difference was demonstrable between OC users and controls in the levels of any of these growth-promoting hormones, nor in plasma concentrations of any of the platelet alpha-granule proteins. The results indicate that the enhanced mitogenicity found in OC sera is most likely not attributable directly to these hormones or PDGF and may instead result from an in vivo OC-induced alteration in other as yet unidentified mediators of cellular growth.
Atherosclerosis 1985 Aug
PMID:The measurement of arterial smooth muscle cell mitogens in the blood of oral contraceptive users. 293 71

Migration of smooth muscle cells from the media to the intima of the arterial wall and proliferation of intimal smooth muscle are major early events in the formation of an atherosclerotic lesion. The start of proliferation requires that the cells have passed through a modulation from contractile to synthetic phenotype and that they are stimulated with growth factors. Here, we have examined the effects of the calcium antagonist nifedipine on phenotypic modulation and growth of isolated rat arterial smooth muscle cells cultivated in vitro. The results indicate that micromolar concentrations of nifedipine slow down the rate of transformation of the cells from a contractile to a synthetic phenotype and inhibit initiation of DNA synthesis as well as cellular proliferation. The inhibitory effect on DNA synthesis was seen both in cells stimulated with whole blood serum and with purified platelet-derived growth factor. The results raise the possibility that nifedipine may be used to prevent atherogenesis and to inhibit progression of fibromuscular lesions by interfering with the proliferation of arterial smooth muscle cells.
Atherosclerosis 1985 Dec
PMID:The calcium antagonist nifedipine inhibits arterial smooth muscle cell proliferation. 300 18

The dramatic rise and equally dramatic fall in the mortality from coronary heart disease in the 20th century is only partly explained. This article reviews the development of our ideas concerning possible pathways other than lipids that might play a role in the development of human atherosclerosis alone or in combination with one or more of the usually considered risk factors. In some instances, such as that of cigarette smoking, the proposed concept regarding genetic alterations in vascular smooth muscle suggests a mechanism for development of at least some of the lesions. Recent studies have shown that an aberration in platelet-derived growth factor gene expression is unlikely to be a factor in proliferation of smooth-muscle cells. Aberrant expression of other oncogenes or some as yet unknown virus remain as possible explanations of some of the incidence of atherosclerosis and its consequent coronary heart disease.
 ...
PMID:Origins of human atherosclerotic plaques. The role of altered gene expression. 305 60


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>