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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is generally recognized that formation of a platelet-fibrin-rich thrombus in an atherosclerotic coronary artery is the basis of unstable angina and acute myocardial infarction. Platelet hyperactivity has been identified in coronary risk factors such as hyperlipidemia and diabetes mellitus. Persistent activation of these cells results in release of growth factors that may contribute to the progression of atherosclerosis. Several recent studies show that endothelium, by generating or metabolizing a host of vasoactive substances, plays a critical role in the modulation of vascular tone. Important among these substances are prostacyclin (PGI2) and endothelium-derived relaxing factor (EDRF). The endothelium-dependent modulation of coronary artery tone correlates with the severity of atherosclerosis and the number of coronary risk factors. Procedures such as angioplasty and coronary bypass surgery injure the endothelium. The loss of endothelial smooth muscle relaxant function may contribute to the vasoconstriction and thrombosis often observed soon after these procedures. Thrombolysis (and subsequent reperfusion of the coronary artery) is also associated with severe endothelial dysfunction, with a resulting vasoconstrictor influence on the coronary vascular bed. Activation of leukocytes and their presence in the reperfused myocardium contribute to progression of myocardial injury by release of oxygen free radicals and proteolytic enzymes. Thus, it seems that a perturbation in this delicate equilibrium in cellular interactions relates to genesis and progression of myocardial ischemia.
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PMID:Platelet-leukocyte-endothelial interactions in coronary artery disease. 154 43

As a source of several vasoactive factors, the endothelium takes part in the regulation of vascular tone. The most important endothelium-derived vasoactive substances are nitric oxide, prostacyclin, endothelin-1 and contracting factors requiring the activity of cyclooxygenase. The endothelium is an obvious target organ of cardiovascular risk factors. Accordingly, functional alterations do occur with aging, hypertension, and lipids. All three conditions are associated with a decreased basal and stimulated release of endothelium-derived nitric oxide. On the other hand, the release of endothelin-1 appears to increase with age, while the sensitivity to the peptide markedly decreases under the same conditions. In the spontaneously hypertensive rat, acetylcholine and stretch evoke the release of cyclooxygenase-dependent endothelium-derived contracting factor, most likely prostaglandin H2. The sensitivity and circulating levels of endothelin-1, on the other hand, are reduced in this experimental model of hypertension. In the porcine coronary circulation, oxidized low-density lipoproteins selectively reduce endothelium-dependent relaxations to aggregating platelets, serotonin, and thrombin which are mediated by nitric oxide. The alterations of endothelial function occurring with aging, hypertension, and hyperlipidemia may have important clinical implications for the pathogenesis of cardiovascular disease.
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PMID:Endothelium-dependent control of vascular tone: effects of age, hypertension and lipids. 195 6

More than a decade has passed since the introduction of the concept that inhibition of platelet function may be helpful in preventing the initiation of thrombus formation. Aspirin has been recognized as inhibiting normal platelet function and the mechanism has been clearly delineated. Legions of patients have been studied to answer the question of whether aspirin is efficacious in the primary prevention of acute myocardial infarction. At the present time, however, a solid, clear answer is not available and firm recommendations cannot be made. A large number of studies evaluating aspirin and other antiplatelet agents in the prevention or delay of recurrent myocardial infarction (secondary prevention) have been completed and those studies reporting a favorable beneficial effect are in the minority. In these secondary prevention studies reporting success, the doses of aspirin employed were large enough to inhibit both the cyclo-oxygenase system and thromboxane A2 production as well as the synthesis of prostacyclin. Thus, in these studies if aspirin is effective in reducing adverse cardiovascular events, its efficacy is being mediated by an unknown mechanism. If the reader of the few studies that report positive results is convinced of the benefit of aspirin, it must be emphasized that thoughtful, cautious patient selection based upon the individual's cardiovascular risk profile must be exercised. Individual variation may exist with respect to aspirin's beneficial effect. It must be absolutely recognized that aspirin or any antiplatelet agent does not in any way substitute for the removal or treatment of coexisting risk factors such as tobacco, obesity, hypercholesterolemia, hyperlipidemia, hypertension, and metabolic disease. In contrast to aspirin, control of the above risk factors has been established as beneficial. Aspirin is not free of undesirable side-effects; fatalities secondary to hemorrhage have been reported, and these must be known in detail and understood by both physician and patient before this agent is prescribed in the prophylactic treatment of cardiovascular disease.
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PMID:Aspirin in the prevention of thrombosis. 203 Jun 40

The obese Zucker rat develops hyperlipidemia, proteinuria and focal glomerulosclerosis without prior changes in renal hemodynamics. To study the effects of oral fatty acid intake on the development of renal injury in this model, rats were fed standard chow or chow supplemented with either 14% fish oil or 14% beef tallow after unilateral nephrectomy at the age of 10 weeks. At 32 weeks post-nephrectomy animals were sacrificed and renal tissue saved to assess histology and glomerular eicosanoid production. Fish-oil treated rats had lower mean plasma cholesterol levels and developed less proteinuria than control or tallow-fed animals although there was no difference in plasma creatinine or blood pressure. Histological analysis showed significantly fewer sclerosed glomeruli in the fish oil group (4.0 +/- 0.8% vs. control 19.4 +/- 4.1%, P less than 0.0005 and vs. beef tallow 10.8 +/- 1.9%, P less than 0.005). Glomeruli derived from rats on fish oil supplements produced smaller amounts of prostaglandin (PG)E2 and of the stable metabolites of PGI2 (6-oxo-PGF1 alpha), PGF2 (PGF2 alpha) and thromboxane (TX)A2 (TXB2) than those from tallow-fed animals. This study demonstrates that oral fatty acid intake may influence the development of glomerulosclerosis. The apparent beneficial effects of fish oil have not been fully defined, but may relate to favorable changes in plasma lipid concentration and renal eicosanoid production.
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PMID:Effects of dietary fatty acids in an animal model of focal glomerulosclerosis. 206 9

A number of experimental studies have reported that dietary fish oil can attenuate the development of atherosclerosis in cholesterol-fed rats, quails, rabbits, pigs, and monkeys. Epidemiologic studies suggest that dietary fish oil can reduce the development of cardiovascular disease in humans. Data are limited but suggest that laboratory animals, normal volunteers, and patients with hyperlipidemia show similar responses to the consumption of fish oil. The major effect of dietary fish oil on serum lipoproteins is a reduction in plasma triglyceride levels, with inconsistent effects on plasma cholesterol and HDL-cholesterol. Dietary fish oil induces a significant reduction of platelet aggregation associated with a prolonged bleeding time. This antithrombotic effect may be partially related to a decreased thromboxane A2 and to an increased prostacyclin level. Dietary fish oil may also have anti-inflammatory and anti-immunologic effects through an elevation of prostaglandins and a reduction in the level of leukotriene B4. Recent experimental data suggest that either fish oil or verapamil can bring on a regression in atherosclerosis in cholesterol-fed rabbits put on a normal diet; however, there was no additive effect of the combination of these agents. Overall, data suggest that fish oil may have a role in attenuating the development of atherosclerosis.
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PMID:Modification of experimental and clinical atherosclerosis by dietary fish oil. 210 47

An increased platelet-vessel wall interaction plays an important role in most forms of cardiovascular disease. In healthy arteries, the vascular endothelium prevents platelet adhesion and aggregation. As a mediator of this protective function, the endothelium produces prostacyclin, endothelium-derived nitric oxide and tissue plasminogen activator. Cardiovascular risk factors such as hypertension, hyperlipidemia and diabetes are associated with an increased platelet activation and with decreased antithrombotic properties of the blood vessel wall. The available inhibitors of platelet function interfere only with one of various mechanisms of platelet activation and of the platelet-vessel wall interaction. Prostaglandin inhibitors, such as aspirin and newer, more specific inhibitors, prevent the production and/or the effect of thromboxane A2 on platelets and the blood vessel wall. Other drugs interfere with the effect of adenosine diphosphate on platelets, or they increase intracellular concentration of cyclic GMP or AMP in platelets and vascular smooth muscle cells. The protective effects of platelet inhibitors in primary and particularly in secondary prevention of cardiovascular diseases have been documented in numerous studies. The successful clinical use of these substances, however, requires a selective prescription of the drugs in patients with cardiovascular disease.
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PMID:[Thrombocyte inhibitors in cardiovascular therapy]. 221 49

New Zealand strain white male rabbits were divided into four groups to study the effects of 8501, extracted from a Chinese herb, on hyperlipidemia and the TXA2/PGI2 ratio in atherosclerotic rabbits. The results indicate that serum cholesterol and the levels of cholesterol and cholesteryl ester in aortic tissue were significantly increased in cholesterol-fed rabbits. The percentage of alpha-lipoprotein was significantly decreased and the aortic atherosclerotic plaque area was significantly increased. The data also demonstrate that the level of plasma TXB2 was markedly increased, while that of 6-keto-PGF1 alpha was significantly decreased. The TXB2/6-keto-PGF1 alpha ratio (T/6) was significantly increased. The decrease of 6-keto-PGF1 alpha occurred prior to the increase of TXB2. Compound 8501 not only lowered serum total cholesterol and aortic total cholesterol and cholesteryl ester but also antagonized the decrease of alpha-lipoprotein and atherosclerotic plaque formation. In addition, 8501 prevented the decrease of plasma 6-keto-PGF1 alpha and the increase of TXB2, and so the T/6 ratio was significantly decreased.
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PMID:Effects of purified compound (8501) on hyperlipidemia and the balance between thromboxane A2 and prostacyclin in rabbits. 229 35

An increased lipid peroxides and a decreased production of prostacyclin have been shown in advanced atherosclerotic lesions and plasma. Our purpose was to determine whether the similar findings could be observed in cultured endothelial cells, and whether antioxidants could protect the cell against peroxide injury. In these experiments we have used bovine aortic endothelial cells in culture to address the issue of hyperlipidemia-induced arterial damage. Results of the present study showed that different concentration of hyperlipidemic sera from atherogenic rabbits induced a time- and dose-dependent alteration in the production of prostacyclin and levels of lipid peroxides in endothelial cells. Endothelial cells incubated with hyperlipidemic serum increased prostacyclin generation significantly during the initial stages and then continuously decreased. When endothelial cells were incubated for 36 h, TXA2 generation was also impaired and at the same time the cellular lipid peroxides content increased. There was a positive correlation between the concentration of hyperlipidemic serum and lipid peroxides and an inverse correlation with prostacyclin synthesis. The medium supplemented with antioxidant selenium or vitamin E showed a significant decrease in lipid peroxides and an increase in prostacyclin synthesis. These results suggest that both hyperlipidemic serum and lipid peroxides injury endothelial cells and inactivate prostacyclin synthetase, resulting in a decrease of prostacyclin production, while antioxidants have a protective effect. We conclude that the increase in lipid peroxides in association with hyperlipidemia results in alteration of prostacyclin synthesis that may play an important role in the pathogenesis of atherosclerosis.
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PMID:Effect of hyperlipidemic serum on lipid peroxidation, synthesis of prostacyclin and thromboxane by cultured endothelial cells: protective effect of antioxidants. 267 46

Endothelial cells can release substances which profoundly affect vascular tone and platelet function. The inhibitory substances include endothelium-derived relaxing factor (EDRF or nitric oxide), prostacyclin and probably an endothelium-derived hyperpolarizing factor. Endothelin is a potent vasoconstrictor peptide released from endothelial cells. Under certain conditions, the endothelium can also produce angiotensin II, thromboxane A2 and a cyclooxygenase-dependent endothelium-derived contracting factor. In normal arteries, the effects of EDRF appear to dominate. In diseased arteries, the release and action of EDRF is impaired and that of endothelium-derived contracting factors is increased. Hyperlipidaemia, atherosclerosis and hypertension reduce endothelium-dependent relaxations. Hypoxia inhibits the release of EDRF and prolonged ischaemia severely impairs the response. Regenerated endothelium at sites of mechanical injury exhibits selective defects in response to aggregating platelets. The more effective release of EDRF in arterial compared with venous bypass grafts further suggests an involvement of the factor in preventing vascular occlusion. Therapeutic interventions with specific drugs and diets can augment the impaired endothelium-dependent relaxation of diseased arteries. Thus, functional changes of the endothelium in coronary artery disease may be an important factor in the development of vasospasm, ischaemia and thrombosis.
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PMID:Endothelium-derived relaxing and contracting factors: potential role in coronary artery disease. 268 Apr 93

Alterations in lipid metabolism occur in patients with chronic renal disease and in patients with the nephrotic syndrome and may have a role in the progression of renal disease in such patients. Evidence accumulated over the last few years indicates that increased ingestion of cholesterol accelerates the development of glomerulosclerosis in guinea pigs, rats and rabbits, and in rats with endogenous hyperlipidemia due to the nephrotic syndrome. Lowering the levels of serum lipids ameliorates the progression of renal disease in obese rats, rats with a remnant kidney and rats with the nephrotic syndrome produced by the aminonucleoside of puromycin. Changes in dietary fatty acids also influence the progression of renal disease. Several eicosanoids influence the progression of renal disease in experimental animals. Maneuvers that decrease the production of thromboxane A2 ameliorate renal disease in rats with a remnant kidney and in mice with lupus nephritis. Increasing the production of vasodilatory prostaglandins (PGE2, prostacyclin) seems to have a beneficial role in the progression of renal disease. The mechanisms by which dietary lipids and/or renal eicosanoids affect the progression of renal disease remain to be defined.
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PMID:Role of dietary lipids and renal eicosanoids on the progression of renal disease. 269 98


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