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)

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

In order to investigate the effect of fenofibrate on microcirculation, 16 patients (5 female, 11 male, age 58 +/- 8 years) were studied with the aid of nailfold capillaroscopy before and after treatment with 200 mg fenofibrate per day over six weeks. Fenofibrate resulted in a significant decrease in triglycerides, total and LDL-cholesterol and apolipoprotein B and an increase in apolipoprotein A. As a parameter of an improved microcirculation the time to peak capillary blood cell velocity during postreactive hyperemia (occlusion of the lower arm for 2 minutes, 200 mmHg) decreased markedly from 45 +/- 5 to 16 +/- 3 s, p < 0.0001). Fibrinogen levels were significantly decreased (p < 0.04) in contrast to other parameters with a possible impact on microvascular perfusion (hemoglobin, hematocrit, mean platelet volume, total protein) and to blood pressure and heart rate. These findings suggest that fenofibrate treatment improves microcirculation in patients with hyperlipidemia. This beneficial effect of fenofibrate may arise from two leading mechanisms. One of these might be the decrease in fibrinogen levels reducing plasma viscosity, the other mechanism might be an indirect effect on functional abnormalities of the vascular endothelium arising from hyperlipdidemia. By lowering plasma lipids fenofibrate is likely to restore the impaired formation or efficacy of the endothelium derived relaxing factor (nitric oxide, NO).
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PMID:Fenofibrate improves microcirculation in patients with hyperlipidemia. 951 68

Hyperlipidemia in the nephrotic syndrome results from increased synthesis and decreased catabolism of lipoproteins. The contribution of each to establishing blood lipid levels is unknown. Increased triglyceride rich lipoprotein concentration, very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) primarily results from decreased clearance. This defect is due in part to reduced lipoprotein lipase (LPL) on the vascular endothelium resulting either from decreased synthesis or inadequate binding of this enzyme to endothelial surfaces. In contrast, both low density lipoprotein (LDL) and lipoprotein(a) [Lp(a)] concentrations are increased. Unlike the case of albumin or transferrin, or apoA-I in the rat, LDL apoB 100 synthesis is not related to that of albumin, suggesting a different mechanism of regulation or a response to a stimulus that is not the same as that augmenting the synthesis of nonlipoproteins. Evidence is presented for synthesis of LDL through a mechanism that bypasses the normal delipidation pathway that requires a VLDL precursor for LDL formation. HDL concentration is normal but maturation is impaired leading to a shift from the larger HDL2 to the smaller HDL3, a variant that is less effective as a transporter of the LPL cofactor apolipoprotein C II.
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PMID:New insights into lipid metabolism in the nephrotic syndrome. 1041 29

Induction of acute pancreatitis follows a uniform mechanism independent of the different etiologic factors such as gallstones, alcohol, ischemia, hyperlipidemia, hypercalcemia, hereditary and others. Each cause seems to affect primarily the acinar cell, resulting in premature intracellular activation of trypsinogen and other digestive enzymes. Activated enzymes and oxygen free radicals injure the acinar cell and cause a release of cytokines and vasoactive mediators, attract inflammatory cells and activate the vascular endothelium as well as the expression of adhesion molecules. The disturbance of the pancreatic microcirculation induces a progression from edematous to necrotizing pancreatitis independent of the early intracellular events, including protease activation. Specific therapy must be directed towards microperfusion failure as a secondary pathogenetic step, since the initial enzyme activation and cytokine release is irreversible by the time of clinical presentation. In experimental designs comparable to the clinical situation the following therapeutic principles have proven beneficial: increase of blood fluidity by dextran, inhibition of leukocyte-endothelium interaction by ICAM-1 antibodies, and blockade of local vasoconstriction by endothelin-receptor antagonists.
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PMID:[New pathophysiologic knowledge about acute pancreatitis]. 1078 41

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

We describe the case of a young HIV-positive patient undergoing three-drug antiretroviral therapy that included a protease inhibitor for 9 months, who was admitted to the hospital with an acute myocardial infarction. A coronary angiogram revealed occlusion caused by a thrombus in the proximal third of the anterior descending artery. Complete recanalization was obtained after an angioplasty was performed. At the time of the infarction, only the triglyceride levels were found to be high. Metabolic alterations associated with the prolonged use of protease inhibitors have been described such as an increase in the triglyceride and cholesterol serum levels, diabetes, resistance to insulin, lipodystrophy, and pancreatitis. The consequences of chronic hyperlipidemia are well known in the medical literature, especially premature coronary artery disease. No family history of coronary artery disease was identified in this patient. Whether the genesis of this localized coronary thrombosis was due to a change in the metabolism of the vascular endothelium caused by the protease inhibitors, or by related dyslipidemia, is still to be determined. In this case, the data suggest a strong link between coronary insufficiency and prolonged use of the protease inhibitor.
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PMID:Acute Myocardial Infarction in a 34-Year-Old HIV-Positive Female Patient While Undergoing Active Antiretroviral Therapy Containing a Protease Inhibitor. 1108 68

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

Mortality is markedly elevated in patients with end-stage renal disease. The leading cause of death is cardiovascular disease. Lipoprotein levels are only slightly elevated in dialysis patients, and cardiovascular risk is inversely correlated with serum cholesterol, suggesting that a process other than hyperlipidemia plays a role in the incidence of cardiovascular disease. Hypoalbuminemia, ascribed to malnutrition, has been one of the most powerful risk factors that predict all-cause and cardiovascular mortality in dialysis patients. The presence of inflammation, as evidenced by increased levels of specific cytokines (interleukin-6 and tumor necrosis factor alpha) or acute-phase proteins (C-reactive protein and serum amyloid A), however, has been found to be associated with vascular disease in the general population as well as in dialysis patients. The process of inflammation, also called the acute-phase response, additionally causes loss of muscle mass and changes in plasma composition-decreases in serum albumin, prealbumin, and transferrin levels, also associated with malnutrition. Inflammation alters lipoprotein structure and function as well as endothelial structure and function to favor atherogenesis and increases the concentration of atherogenic proteins in serum, such as fibrinogen and lipoprotein (a). Inflammation in dialysis patients is episodic. The causes are likely to be multifactorial and include vascular access infection, less-than-sterile dialysate, dialysate back leak, and nonbiocompatible membranes in addition to clinically apparent infection. In addition, proinflammatory compounds, such as advanced glycation end products, accumulate in renal failure, and defense mechanisms against oxidative injury are reduced, contributing to inflammation and to its effect on the vascular endothelium.
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PMID:The microinflammatory state in uremia: causes and potential consequences. 1142 86

Diabetes-associated oxidative stress is clearly manifest in peripheral nerve, dorsal root, and sympathetic ganglia of the peripheral nervous system and endothelial cells and is implicated in nerve blood flow and conduction deficits, impaired neurotrophic support, changes in signal transduction and metabolism, and morphological abnormalities characteristic of peripheral diabetic neuropathy (diabetic peripheral neuropathy). Hyperglycemia has a key role in oxidative stress in diabetic nerve, whereas the contribution of other factors, such as endoneurial hypoxia, transition metal imbalance, and hyperlipidemia, has not been rigorously proven. It has been suggested that oxidative stress, particularly mitochondrial superoxide production, is responsible for sorbitol pathway hyperactivity, nonenzymatic glycation/glycooxidation, and activation of protein kinase C. However, this concept is not supported by in vivo studies demonstrating the lack of any inhibition of the sorbitol pathway activity in peripheral nerve, retina, and lens by antioxidants, including potent superoxide scavengers. Its has been also hypothesized that aldose reductase (AR) detoxifies lipid peroxidation products, and therefore, the enzyme inhibition in diabetes is detrimental rather than benefical. However, the role for AR in lipid peroxdation product metabolism has never been demonstrated in vivo, and the effects of aldose reductase inhibitors and antioxidants on diabetic peripheral neuropathy are unidirectional, i.e., both classes of agents prevent and correct functional, metabolic, neurotrophic, and morphological changes in diabetic nerve. Growing evidence indicates that AR has a key role in oxidative stress in the peripheral nerve and contributes to superoxide production by the vascular endothelium. The potential mechanisms of this phenonmenon are discussed.
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PMID:How does glucose generate oxidative stress in peripheral nerve? 1219 15

In order to observe the anti-atherosclerosic effect of the grape seed extract and its mechanism, the 50C57/6J mice are divided randomly into 5 group (normal control group, hyperlipidemia model group, low and high grape seed extract groups(0.2 mg/gBW, 0.6 mg/gBW), and drug control group(0.2 mg/gBW). After twenty-one weeks, plasma oxidized low density lipoprotein (OX-LDL), serum nitric oxide (NO) and intercellular adhesion molecule-1 (ICAM-1) are measured and the form of aortic valves are observed pathologically. The results show that the levels of plasma OX-LDL, and ICAM-1 are significantly lower in grape seed extract group than those in model group while the levels of NO are higher in grape seed extract group than that in model group (P < 0.01). The thickness of aortic valves consisting of foam cell and endothelium hyperplasia in grape seed extract group is lighter than that of model group. The results indicate that the grape seed extract has inhibitary effect on atherosclerosis in C57BL/6J mice, and the possible mechanism may be related to inhibition of the increase of OX-LDL, and ICAM-1, reduction of the damage of vascular endothelium and protection of the function of vascular endothelium.
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PMID:[Study of anti-atherosclerosic effect of grape seed extract and its mechanism]. 1260 36


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