Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with glycogen storage disease type 1 (GSD-1) often have marked hyperlipidaemia with abnormal lipoprotein profiles. This metabolic abnormality improves, but is not fully corrected, with dietary therapy and therefore these patients may be at high risk for the development of atherosclerosis. Endothelial dysfunction is an early event in atherogenesis and can be detected in children and young adults at high risk. We studied endothelial function, using a non-invasive ultrasonographic method, in the brachial arteries of 6 adult GSD-1a patients (aged 23-33 years) with mean cholesterol of 7.9 mmol/l (range 4.7 to 14.6) and mean triglycerides of 9.1 mmol/l (range 4.1 to 21.3), and 12 age- and sex-matched normolipidaemic controls. Flow-mediated (endothelium-dependent) dilation was similar in patients and controls (8.2% vs. 10.5%; P = 0.20). Although the patient numbers are small, these results are consistent with the surprising lack of clinically evident atherosclerosis in GSD-1. The reasons these patients appear less susceptible to the damaging arterial effects of hyperlipidaemia are unknown. These results may have implications for others with secondary hyperlipidaemias.
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PMID:Hyperlipidaemia does not impair vascular endothelial function in glycogen storage disease type 1a. 785 75

Endothelial dysfunction appears to be an early event in most forms of cardiovascular disease. The dysfunction may involve a decreased formation, inactivation, or action of nitric oxide or prostacyclin as well as an increased formation of contracting factors, eg, prostaglandin H2 and endothelin-1. Cardiovascular drugs can improve endothelial function either indirectly through their effects on cardiovascular risk factors, such as hypertension, hyperlipidemia, and diabetes or directly through endothelial actions. Direct and indirect endothelial protective effects of cardiovascular drugs may significantly contribute to normal organ perfusion and a reduced incidence of myocardial infarction, stroke, and renal failure in patients. Endothelium-dependent vascular regulation in health and in various cardiovascular diseases as well as the effects of currently available cardiovascular drugs are reviewed.
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PMID:Possibilities and perspectives of pharmacotherapy for endothelial protection. 792 59

New evidence suggests an interaction between hyperlipidemia, activation of the renin-angiotensin system, and atherosclerotic disease. In patients with atherosclerosis and hyperlipidemia, coronary endothelial dysfunction is usually diffuse and affects vasomotor tone, platelet activity, thrombosis, fibrinolysis, and regulation of inflammatory cells. Angiotensin II, an important oxidant, alters the binding of low-density-lipoprotein (LDL) cholesterol to its receptors and increases endothelial uptake of LDL. Endothelial dysfunction is worsened by the suppression of nitric oxide production and/or release via angiotensin II-associated degradation of bradykinin and oxygen free radical production, resulting in inadequate vasorelaxation. Therapy with angiotensin-converting enzyme (ACE) inhibitors appears to eliminate these untoward effects and may ameliorate the tendency for myocardial infarction associated with elevated plasma levels of angiotensin II. Although the role of ACE inhibitors in the prevention and/or treatment of coronary artery disease in patients without left ventricular dysfunction remains to be established, the capacity of ACE inhibition to correct endothelial dysfunction offers promise. The ability of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors to improve endothelial function, prevent the progression of coronary atherosclerosis, reduce the incidence of ischemic events, and improve survival is well known. Potentially, ACE inhibitors may have an additive or synergistic effect on the development of atherosclerosis and the clinical consequences of this disease when used in combination therapy with lipid-lowering strategies.
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PMID:The potential use of angiotensin-converting enzyme inhibitors in patients with hyperlipidemia. 912 18

The generation of nitric oxide by the vascular endothelium maintains a continuous vasodilator tone that is essential for the regulation of blood flow and blood pressure. Nitric oxide also contributes to the control of platelet aggregation and has important antiatherogenic effects. These properties are mediated by the action of constitutive nitric oxide synthase and subsequent activation by nitric oxide of soluble guanylate cyclase. Impaired release of nitric oxide occurs in most animal and human models of hypertension, contributing to the increased peripheral resistance and most likely to the development of cardiovascular complications. Antihypertensive medications (angiotensin-converting enzyme [ACE] inhibitors and calcium channel blockers) appear to prevent the impairment of nitric oxide-mediated vasodilation in experimental hypertension, though in humans the data are not as clear. Reduced nitric oxide release appears therefore to be a consequence rather than a cause of high blood pressure, and the reduction in blood pressure per se is most important. In hyperlipidaemia, endothelium-dependent relaxations are reduced probably due to the inhibitory action of oxidized low-density lipoproteins on endothelium-dependent relaxations. Lipid-lowering strategies and, more recently, ACE inhibition have been demonstrated to improve nitric oxide dependent coronary vasodilation in hypercholesterolaemic patients with and without atheromatous coronary disease. Nitric oxide dependent vasodilation is also impaired in insulin- and non-insulin-dependent diabetes as well as in healthy aging. Endothelial dysfunction may be improved in non-insulin-dependent diabetes by administration of the antioxidants, supporting the hypothesis that nitric oxide inactivation by oxygen-derived free radicals contributes to abnormal vascular reactivity in diabetes.
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PMID:Impairment and restoration of nitric oxide-dependent vasodilation in cardiovascular disease. 948 1

Endothelial dysfunction is a major pathophysiological consequence of hypercholesterolemia and other conditions. We examined whether a synthetic mediator of lipid transport from peripheral tissues to the liver (ie, the "reverse" pathway) could restore normal endothelial function in vivo. Using assays of macrovascular and microvascular function, we found that genetically hypercholesterolemic apolipoprotein E knockout mice exhibited key endothelial impairments. Treatment of the mice for 1 week with daily intravenous bolus injections of large "empty" phospholipid vesicles, which accelerate the reverse pathway in vivo, restored endothelium-dependent relaxation, leukocyte adherence, and endothelial expression of vascular cell adhesion molecule-1 to normal or nearly normal levels. These changes occurred despite the long-standing hyperlipidemia of the animals and the persistence of high serum concentrations of cholesterol-rich atherogenic lipoproteins during the treatment. Our results indicate that dysfunctional macrovascular and microvascular endothelium in apolipoprotein E knockout mice can recover relatively quickly in vivo and that accelerated reverse lipid transport may be a useful therapy.
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PMID:Rapid restoration of normal endothelial functions in genetically hyperlipidemic mice by a synthetic mediator of reverse lipid transport. 1076 69

Chronic renal failure (CRF) is associated with a 20-fold increased risk of cardiovascular death, two principal mechanisms being: sudden, arrhythmic death associated with left ventricular hypertrophy, and ischaemic heart disease, associated with accelerated atherosclerosis. In recent years, the vascular endothelium has been recognised as a large and complex endocrine organ, with many important physiological functions including the control of vascular tone. Endothelial dysfunction, commonly characterised by reduced production of the vasodilator nitric oxide (NO), is thought to be a key initial event in the development of atherosclerosis and is present in patients with hypertension and hyperlipidaemia. While these cardiovascular risk factors are also prevalent in CRF, other factors more specific to uraemia such as accumulation of homocysteine and asymmetric dimethylarginine (endogenous inhibitor of NO synthase) may impair endothelial function. Modulation of endothelial function in CRF may offer a novel strategy to reduce cardiovascular disease.
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PMID:The vascular endothelium in chronic renal failure. 1085 70

Recent reports of myocardial infarctions in young persons infected with human immunodeficiency virus (HIV) who are receiving protease inhibitor therapy have raised concerns about premature coronary artery disease in this population. Endothelial dysfunction, hypercoagulability, hypertriglyceridemia, and abnormal coronary artery pathology were in fact associated with HIV infection prior to the availability of protease inhibitor therapy. Newly recognized risk factors, such as insulin resistance, hypercholesterolemia, and fat redistribution syndrome, may exacerbate underlying atherosclerotic risk for patients receiving protease inhibitors. Data on the incidence of myocardial infarction among these patients are largely limited to case reports but are of concern. Pending the availability of further data, it is prudent to monitor these patients for hyperlipidemia and consider interventions to modify cardiac risk factors.
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PMID:Coronary artery disease and human immunodeficiency virus infection. 1101 31

The endothelium lines all blood vessels in the human body, it is the basic structure which ensures the action of substances circulating in the blood stream on the vascular wall. It is an organ the sound state of which is essential for the physiological function of the vascular system. Its impaired function is a basic factor in the genesis and development of vascular disease. Under physiological conditions the endothelium has antiadhesive and antithrombotic properties, it produces vasoactive substances, prevents the penetration of circulating substances and formed elements across the vascular wall, and via adhesion molecules it participates in the interaction with cells in the circulation. Risk factors of cardiovascular diseases such as hypertension, hyperlipidaemia, hyperglycaemia, smoking damage the function of endothelial cells and cause the development of endothelial dysfunction. In patients with arterial hypertension endothelial dysfunction is characterized by an impaired endothelium dependent relaxation, increased adhesion and permeability of endothelial cells, structural changes of the vascular wall. When the endothelium is damaged by released cytokines an increased expression of adhesion molecules occurs, adhesion and migration of inflammatory cells across the vascular wall. Cytoadhesion molecules are released from the surface of the endothelium into the circulation where the rise of their plasma levels can serve as a marker of endothelial damage. Endothelial dysfunction in hypertonic subjects contributes in a significant way to the development and progression of chronic vascular disease--atherosclerosis. Improvement of the damaged endothelial function is therefore at present a desirable therapeutic objective in the treatment of hypertension.
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PMID:[Endothelial dysfunction and arterial hypertension]. 1104 86

Endothelial dysfunction and changes in arterial wall morphology including thickening of the tunica intima, excess synthesis of collagenous matrix (fibroblastic intimal thickening) and permanent or dynamic deposition of lipids (fatty streaks) already occur in childhood or adolescence. Definite atherosclerotic plaques in the carotid arteries usually do not manifest themselves before menopause in women or age 40 in men. Obviously, cumulative (long-term) and excessive exposure of the vessel wall to risk factors is required to overcome highly effective defense mechanisms which have not yet been fully investigated. Initiation and early progression of atherosclerosis rely on conventional vascular risk factors such as hyperlipidemia, hypertension, smoking, severe alcohol consumption and chronic infections. Plaque extension is effectively compensated by a focal widening of the vessel, thereby preventing the development of lumen obstruction (vascular remodeling). For stenosis to emerge conventional plaques must convert to complicated plaques characterized by plaque rupture and consecutive atherothrombosis. This process usually starts with small- to medium-sized plaques. Potential determinants of plaque rupture are the composition of the lesion (large lipid-rich core), damage of the fibrous cap (destabilization by chronic inflammation) and hemodynamic stress. According to pathological observations, fissuring of atherosclerotic lesions is a frequent event, while the formation of overlying large thrombi (with progression of stenosis or vessel occlusion) is definitely rare. This conjecture emphasizes the significance of local and systemic thrombus-promoting factors. Actually, the risk profile of advanced atherogenesis in the Bruneck Study was primarily composed of markers of enhanced prothrombotic capacity, attenuated fibrinolysis and clinical conditions known to interfere with coagulation. Almost all subjects with > or =3 procoagulant risk conditions developed carotid stenosis or showed progression of preexisting stenosis during a 5-year period. Increasing insights into the complex biology of arterial atheroma and awareness of the etiologic peculiarities of advanced complicated plaques may serve as a basis for identifying high-risk subjects and for novel vascular prevention strategies with focus on plaque stabilization and antithrombotic/anticoagulant measures.
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PMID:Biology of arterial atheroma. 1109 78

Diabetes mellitus and impaired glucose tolerance are linked to increased cardiovascular morbidity and mortality. Vascular disease is directly associated with plasma glucose levels, and reduction of these levels forestalls to a certain extent the vascular complications of diabetes, such as myocardial infarction, nephropathies, and retinopathies. In addition to hyperglycemia, there are other risk factors that play a prominent role, such as hypertension, hyperlipidemia, and genetic factors. Endothelial dysfunction is one of the major factors in the development of cardiovascular disease. The vascular endothelium regulates the blood flow by tightly controlling the coagulation system, cell-cell interaction, and vascular tone. These functions are disturbed in diabetic patients. In diabetics, endothelin-1 levels are increased, leading to vasoconstriction. Endothelin levels are directly related to plasma glucose levels. In addition, the endothelial cell-NO axis is disturbed. NO release and function are impaired. This seems to be dependent upon hyperglycemia and genetic factors. Impaired NO function also results in vasoconstriction. Furthermore, enhanced vascular permeability is seen in diabetics. This appears to be related to impaired endothelial cell relaxation and reactive oxygen species as well as advanced glycosylated end products (AGEs). The complex changes seen in diabetes and even prediabetes are therefore related to numerous derailments related to endothelial dysfunction, and no single therapeutic approach is likely to solve the problem of vascular complications.
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PMID:Endothelial dysfunction in diabetes mellitus. 1112 6


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