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

Both cardiovascular diseases such as hypertension and atherosclerosis and metabolic disorders such as diabetes mellitus and hyperlipidemia are closely related with obesity. In recent studies, superoxide is supposed to play an important role in pathogenesis of the cardiovascular diseases. Superoxide inhibits the biological action of nitric oxide, known as endothelium-derived relaxing factor, leading to vasoconstriction. Moreover, superoxide directly affects the functions of endothelial cells and vascular smooth muscle cells. It has been investigated that the metabolic disorders associated with obesity enhance the superoxide production in the arterial walls through the insulin resistance. In hyperglycemic state, the production of superoxide is stimulated and the superoxide dimustase is inhibited by non-enzymatic glycation, known as Maillard reaction. Hyperlipidemia also increases endothelial superoxide production. Superoxide may act a key role in relationship between the cardiovascular diseases and the metabolic disorders associated with obesity.
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PMID:[The role of superoxide in relationship between the cardiovascular diseases and the metabolic disorders associated with obesity]. 1094 18

Vascular disease and vasomotor responses are largely influenced by oxidant stress. Superoxide is generated via the cellular oxidase systems, xanthine oxidase, and NADH/NADPH oxidases. Once formed, superoxides participate in a number of reactions, yielding various free radicals such as hydrogen peroxide, peroxynitrite, oxidized low-density lipoprotein, or hypochlorous acid. Numerous cellular antioxidant systems exist to defend against oxidant stress; glutathione and the enzymes superoxide dismutase and glutathione peroxidase are critical for maintaining the redox balance of the cell. However, the redox state is disrupted by certain vascular diseases. It appears that oxidant stress both promotes and is induced by diseases such as hypertension, atherosclerosis, and restenosis as well as by certain risk factors for coronary artery disease including hyperlipidemia, diabetes, and cigarette smoking. Once oxidant stress is invoked, characteristic pathophysiologic features ensue, namely adverse vessel reactivity, vascular smooth muscle cell proliferation, macrophage adhesion, platelet activation, and lipid peroxidation.
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PMID:Oxidant stress in the vasculature. 1112 5

Endothelial function is abnormal in a variety of diseased states such as hypercholesterolemia and atherosclerosis. This may be secondary to decreased synthesis of nitric oxide (NO) and/or increased degradation of NO due to interaction with superoxide anions. More recent experimental observations demonstrate increased production of superoxide in hyperlipidemia, suggesting that endothelial dysfunction in these states is in part secondary to increased NO metabolism. Enzymes proposed to be involved in increased superoxide production may include xanthine oxidase, the NO synthase, and the NAD(P)H oxidase. Superoxide rapidly reacts with NO to form peroxynitrite (ONOO-), a highly reactive intermediate with cytotoxic properties. Despite experimental evidence for the oxidative stress concept in causing endothelial dysfunction, the results of recent randomized trials to test the influence of antioxidants on coronary event rates and prognosis in patients with coronary artery disease were very disappointing. In all of these studies the use of vitamins such as vitamin E failed to improve the prognosis. In contrast, treatment with angiotensin converting enzyme inhibitors or cholesterol- lowering drugs improved endothelial dysfunction, prevented the activation of superoxide-producing enzymes in cholesterol-fed animals, reduced coronary event rates, and improved prognosis in patients with coronary artery disease. Therefore, inhibition of superoxide production at the enzymatic level rather than symptomatic superoxide scavenging may be the better choice of treatment.
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PMID:Antioxidants and endothelial dysfunction in hyperlipidemia. 1117 9

We have done consecutive studies to investigate the effects of impaired lipid metabolism on the contractile and relaxation response of cavernous smooth muscles and to elucidate its pathogenesis: 1) incidence of hyperlipidemia in impotent patients; 2) erection response to intracavernous injection of papaverine in impotent patients with hyperlipidemia; 3) relaxation responses of isolated cavernosal smooth muscles to endothelium-independent and endothelium-dependent vasodilators in impotent patients with hypercholesterolemia or hypertriglyceridemia; 4) involvement of superoxide radical in the impaired endothelium-dependent relaxation of cavernous smooth muscle in hypercholesterolemic rabbits; 5) effects of isolated lipoproteins and triglyceride, combined oxidized LDL plus triglyceride, and combined oxidized LDL plus HDL on contractile and relaxation response of rabbit cavernous smooth muscles; 6) involvement of e-NOS in the impaired endothelium-dependent relaxation of cavernous smooth muscle in hypercholesterolemic rabbit. Hypercholesterolemia may cause impairment of endothelium-dependent relaxation. Oxidized LDL is the major causative cholesterol of the impaired relaxation response. A chain reaction, the production of superoxide radicals and functional impairment of eNOS may be a major cause of the functional impairment in the early stages of hypercholesterolemia.
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PMID:Hyperlipidemia and erectile dysfunction. 1122 73

Endothelial dysfunction has been proposed as an early manifestation of atherosclerosis. The risk for atherosclerosis is increased in patients with diabetes mellitus, but the mechanism of the increased risk in these patients remains to be elucidated. Emerging evidence suggests that postprandial hyperglycaemia and hyperlipidemia are important risk factors in the development of atherosclerosis in patients with diabetes. Using a high-resolution ultrasound technique, we evaluated the acute effects of oral glucose loading on endothelium-dependent flow-mediated dilation (EFMD) and endothelium-independent flow-mediated dilation (EIFMD) of the brachial artery in 11 men (mean age: 59 +/- 5 years) with type 2 diabetes without chronic complications of diabetes. During these examinations, changes in the level of superoxide anion formation in the neutrophils were also measured. In addition, to investigate the relationship between acute hypertriglyceridemia and EFMD, we assessed the effects of high- and low-fat meals on EFMD of the brachial artery in 12 healthy volunteers. EFMD was diminished after glucose loading (13.2% +/- 6.4%, 7.3% +/- 3.3%*, 12.8% +/- 5.6%, in fasting and at 1 and 2 hours, respectively; *P<0.001 vs fasting). Superoxide anion formation by neutrophils (expressed as 10(-7) nmol/10(6) cells/30 min) was increased after glucose loading (4.7 +/- 2.8 and 6.2 +/- 2.2, in fasting and at one hour, respectively; P<0.05). EIFMD and triglyceride concentrations were not significantly affected by glucose loading. EFMD was also decreased by high-fat feeding (13.1% +/- 4.3%, 7.7% +/- 3.7%*, 7.3% +/- 2.2%*, basal, 2 hours, and 4 hours, respectively; *P<0.01 vs basal). These decreases were reversed by vitamin E treatment. These results show that acute hyperglycaemia induced by 75 gm oral glucose intake and acute hypertriglyceridemia induced by high-fat feeding are implicated in endothelial dysfunction. In addition, these results suggest that chronic and repeated hyperglycaemia and hypertriglyceridemia may play important roles in the development and progression of vascular complications in diabetes, probably through increased oxidative stress.
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PMID:Endothelial dysfunction: its relationship with acute hyperglycaemia and hyperlipidemia. 1216 9

The endothelial cell layer displays the features of a distributed organ and has a variety of biological functions such as keeping the balance between coagulation and fibrinolysis, expression of adhesion molecules for cells in the immune system, metabolism of noradrenaline and 5-hydroxytryptamine, and conversion of angiotensin I and bradykinin. The endothelium also regulates the underlying smooth muscle layer and vascular tone by release of endothelium-derived relaxing factors such as nitric oxide (NO), prostaglandins, and endothelium-derived hyperpolarizing factor (EDHF) as well as vasoconstricting factors such as endothelin, superoxide (O(2)(-)), and thromboxane. We have reviewed the nature, mechanisms of action, and role of these factors in regulation of vascular tone, with special emphasis on NO. By a process catalyzed by NO synthase, NO and citrulline is formed from the substrates molecular O(2) and L-arginine. The main receptor for NO is guanylyl cyclase leading to formation of smooth muscle cyclic guanosinmonophosphate and relaxation. EDHF is an endothelium-derived factor causing vasorelaxation of the underlying smooth muscle layer by hyperpolarization. The nature of EDHF is still unknown, but several candidates for EDHF have been proposed such as potassium ions, hydrogen peroxide, and epoxyeicosatrienoic acids. Prostaglandins such as prostacyclin and prostaglandin E2 binds to specific receptors followed by increases in cyclic adenosinmonophosphate and vasorelaxation, while contractile prostaglandins constrict vessels by activation of thromboxane and endoperoxidase receptors. Superoxide anions induce contraction of vascular smooth muscles cells by scavenging NO. Endothelin is a potent endothelium-derived contractile factor. The synthesis of endothelin-1 is induced by hypoxia, thrombin, interleukin-1, transforming growth factor-beta1, vasopressin, and catecholamines. Cardiovascular risk factors like age, hypertension, and hyperlipidemia are associated with impaired endothelium-dependent vasodilation either as a consequence of increased inactivation of endothelium-derived vasodilators or increased formation of endothelium-derived contracting factors. This imbalance of endothelium-derived factors plays a role for development of atheroslerosis and ischemic vascular diseases.
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PMID:[Role of nitric oxide and other endothelium-derived factors]. 1273 1