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 progression of atheroarteriosclerosis was shown to be age dependent. This designation covers two separate entities: arteriosclerosis, the progressive and diffuse hardening of the walls of arteries with loss of elasticity, and atheromatous plaque formation, which can start early in life according to nutrition and genetic factors (LDL-receptor expression). Lipoprotein-receptor interactions play a crucial role in lipidic plaque formation. There is, however, no indication that the diffuse hardening of the vascular wall would also be influenced by these mechanisms. We described recently a high-affinity receptor for elastin peptides, present on smooth muscle cells, fibroblasts, and also on monocytes and PMNs. When activated, this receptor will increase intracellular calcium. Circulating elastin peptides were determined by a sensitive Elisa method and found to be between 0.1 and 20 micrograms/ml, in the range of activation of the elastin receptor. They increase in obliterative arteriopathies and type IIb hyperlipidemia. Elastolysis accompanies aging and vascular pathology; the sensitivity of this receptor changes with age, intracellular Ca++ increases, but the receptor appears to be uncoupled from its normal transmission mechanism. These results may well explain the increasing diffuse calcification of the vessel wall. The previously demonstrated potentiation of cholesterol deposition in elastic fibers by calcium is in agreement with simultaneous deposition of calcium and lipids. The recent demonstration of the efficient competition of fibronectin for LDL in proteoglycan-LDL complexes suggests that this reaction may be involved in foam cell formation by the opsonization of LDL for phagocytosis. Fibronectin was shown to accumulate in atherosclerotic plaques. Altogether these recent results confirm the importance of cell-matrix interactions in atherogenesis and lead to a better understanding of the age dependence of these disease processes.
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PMID:Cell-matrix interactions in the genesis of arteriosclerosis and atheroma. Effect of aging. 133 48

HYPERTENSION AND RENAL DISEASE: In experimental models of renal disease not only protein intake and hyperlipidaemia but also hypertension may contribute to the progressive deterioration in renal function; in these models an imbalance in intrarenal haemodynamics appears to be a particularly important factor. ANTIHYPERTENSIVE THERAPY: A reduction in arterial pressure can alter the course of human chronic renal disease. However, it is not clear whether any one class of antihypertensive drug is superior to any other class in these patients. Angiotensin converting enzyme (ACE) inhibitors may prevent the progression from incipient to overt diabetic nephropathy and afford better protection than conventional treatment. In patients with non-diabetic renal disease there is no unequivocal evidence for a protective effect. In renal transplant recipients, mainly those taking cyclosporine, ACE inhibitors are equally effective compared to calcium antagonists in the control of hypertension, but their renal effects in transplant recipients without renal artery stenosis have not yet been assessed.
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PMID:Antihypertensive therapy in renal disease and transplantation. 140 37

The incidence of end-stage renal disease is increasing and this results in an enhanced requirement of renal replacement therapy facilities. This brings about a significant burden on health care budgets and makes strategies that slow down or even prevent deterioration of the renal function mandatory. Although large scale randomized, controlled and prospective clinical trials on the effect of blood pressure control on the course of renal function are lacking, there is circumstantial evidence from animal, epidemiological and clinical studies to state that treatment of hypertension to blood pressure values well within the normal range is most important to ameliorate the downhill course of renal function in patients with chronic renal failure. Moreover, treatment of hypertension is critical to reduce morbidity and mortality of cardiovascular disease in these patients, who have an increased risk for such events. Low-protein diets, if possible with ketoacid supplement, are advocated to slow down the deterioration of renal function. However, based on the results of recent studies, low-protein diets may only have a moderate effect in patients with diabetic nephropathy and, possibly, in patients with chronic glomerulonephritis. The possibility of influencing renal ammoniagenesis by protein restriction or calcium carbonate administration, and an attenuation of alternative complement pathway activation and tubulo-interstitial injury, are challenging. Finally, in animal studies it has been found that abnormalities in serum lipid profile contribute to the progression of chronic renal failure, which may be prevented by pharmacological treatment of hyperlipidemia. Studies in humans concerning this subject are lacking at this moment, but treatment of hyperlipidemia is proper to reduce cardiovascular events.
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PMID:Clinical strategies for arresting progression of renal disease. 140 61

Under certain circumstances the effect of insulin to promote glucose uptake in peripheral tissues is reduced because of a resistance to insulin action. This insulin resistance and the resulting hyperinsulinaemia are now recognised as common background factors that may be responsible for hypertension, hyperlipidaemia, decreased thrombolysis and also impaired glucose tolerance and diabetes. Hyperinsulinaemia has also been identified as an independent risk factor for coronary heart disease and promotes smooth muscle cell growth and plaque formation. A series of studies have now demonstrated that treatment with selective beta-blockers as well as thiazide diuretics impair insulin sensitivity by 15-30% and causes a compensatory increase in insulin concentrations. Furthermore, lipoprotein concentrations are affected in an unfavourable way. This is in contrast to the drugs belonging to ACE-inhibitors, calcium-channel blockers and alpha 1-blocker classes that are either neutral or may have the opposite effects in these respects.
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PMID:Insulin resistance and cardiovascular drugs. 154 Oct 35

We evaluated the effect of a low level of hyperlipidemia and the effects of in vitro exposure to atherogenic lipoproteins (LDL, VLDL) on the vascular responsiveness of isolated porcine coronary arteries. Firstly we studied the change in vascular responsiveness induced by feeding a cholesterol-rich diet to pigs for 4 and 9 weeks (C4 and C9 pigs). The serum cholesterol level in pigs fed a cholesterol-rich diet reached 218.5 +/- 32.9 mg/dl compared with 85.5 +/- 8.4 mg/dl in the controls. Segments of the left descending coronary artery were examined. The contraction induced by KCl or prostaglandin F2 alpha was not altered significantly by hypercholesterolemia nor was the relaxation induced by the Ca2+ ionophore, A23187, or by nitroglycerin. Endothelium-dependent relaxation (EDR) evoked by high, but not low, concentrations of bradykinin was reduced in the C4 pigs as compared with those in normal animals. EDRs evoked by bradykinin, substance P, and serotonin were significantly reduced in C9 pigs. Histologically, as observed by light and electron microscopy, fatty changes or intimal thickenings were not seen in the coronary arteries of the C4 pigs. Minimal changes (intimal thickening and fragmentation of internal elastic lamina) were observed only in parts of arteries of the C9 pigs. Secondly, the direct effects of LDL and VLDL on vascular responsiveness were studied. Although preincubation with LDL inhibited the EDR caused by exposure to bradykinin and A23187 in the coronary arteries of normal and cholesterol-fed pigs, preincubation with LDL inhibited the arterial relaxation induced by exposure to substance P or serotonin in both the C4 and the C9 pigs, but not in the control animals. The degree of inhibition was especially marked in the C9 pigs. The inhibitory effect of VLDL on EDR was weaker than that of LDL. Indomethacin (5 microM) did not alter this inhibitory effect of lipoproteins. Neither LDL nor VLDL had any effect on the vascular relaxation induced by nitroglycerin. These results are consistent with the idea that endothelium-dependent arterial relaxation is attenuated even at the very early stage of cholesterol-induced atherosclerosis. Atherogenic lipoproteins may further impair the decreased EDR in the arteries of hyperlipidemic pigs by two factors: one released on stimulation with bradykinin and the calcium ionophore A23187, the other released on stimulation with substance P and serotonin.
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PMID:Low level hyperlipidemia impairs endothelium-dependent relaxation of porcine coronary arteries by two mechanisms. Functional change in endothelium and impairment of endothelium-dependent relaxation by two mediators. 171 35

There is evidence that hypertensive patients frequently have other metabolic disorders, such as hyperlipidemia and diabetes mellitus. It is also known that the reduction in high blood pressure alone, disregarding the other cardiovascular risk factors, is unable to reduce mortality to the level of the general population. Moreover, the occurrence of metabolic side effects with some antihypertensive drugs deserves particular attention in the treatment of hypertension. Calcium antagonists seem to be devoid of untoward metabolic effects. In particular, several studies have shown that nitrendipine does not deteriorate glucose tolerance. We have evaluated the effects of nitrendipine on insulin response to i.v. glucose load: no change was observed after 2 months of treatment in both serum insulin levels and glucose percent removal rate in comparison to pretreatment values. No unfavorable change was detectable in the studies aimed at investigating the effects of nitrendipine on lipid metabolism parameters. We observed a 22% increase of the percent removal rate of a lipid emulsion (Intralipid) after nitrendipine (3.11 +/- 1.0 vs. 3.80 +/- 1.0%/min, p less than 0.03). This finding suggests a favorable effect of nitrendipine on triglyceride catabolism, possibly mediated by an interference with lipoprotein lipase activity. The metabolic neutrality of nitrendipine, therefore, leads to considering the usefulness of this drug in an antihypertensive treatment that should not disregard the global risk profile.
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PMID:Metabolic neutrality in nitrendipine therapy. 172 52

Exogenous obesity is characterized hemodynamically by expanded intravascular (plasma) volume associated with an increased cardiopulmonary volume and cardiac output. In contrast, essential hypertension is related to an increased total peripheral resistance that is more or less uniformly distributed throughout the component organ circulations associated with a contracted plasma volume in proportion to the height of arterial pressure. Thus, both cardiac output and total peripheral resistance are elevated in obesity hypertension, and both impose a load on the left ventricle, resulting in both a volume and a pressure overload left ventricular hypertrophy. Although renal vascular resistance is not as increased as it is in lean hypertensive patients, these patients are subjected to hyperfiltration and proteinuria. Additionally, these hemodynamic alterations coexist with carbohydrate intolerance, hyperinsulinemia, hyperlipidemia, and hyperuricemia. With weight reduction and associated pressure reduction, the hemodynamic and metabolic changes reverse toward normal. However, should this not be achievable, the angiotensin converting enzyme inhibitors and calcium antagonists provide rational physiological approaches to drug therapy. With these agents pressure reduction is achieved through a fall in vascular resistance without intravascular volume expansion, and this is associated with reduced left ventricular mass and preserved cardiac and renal function, and without exacerbation of preexisting metabolic perturbations. Hence, these two classes of antihypertensive agents may provide a rational and physiological means for reversing the pathophysiological alterations of hypertensive disease in those obese patients in whom weight control is not possible.
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PMID:Obesity hypertension. Converting enzyme inhibitors and calcium antagonists. 173 Apr 48

The effect of lacidipine, a dihydropyridine calcium antagonist on lipid metabolism, has been followed in 8 patients with uncomplicated mild to moderate essential hypertension treated for up to 14 months. There were significant reductions in the systolic and diastolic pressures, from 167/102 to 146/91 mm Hg at 2 months, and to 137/85 mm Hg at the end of the study. Blood lipid concentrations did not change during the observation period (cholesterol 5.1 vs 5.3 mmol.l-1, triglycerides 1.1 vs 1.0 mmol.l-1, HDL-cholesterol 1.1 vs 1.2 mmol.l-1). The results show that lacidipine did not affect lipid metabolism and suggest that calcium antagonists may be safely prescribed for a prolonged period to patients with combined hypertension and hyperlipidaemia.
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PMID:Effect of lacidipine, a long-acting calcium antagonist, on hypertension and lipids: a 1 year follow-up. 174 41

Type-I-patients with silent myocardial ischemia (SMI) have a 2-4fold higher longterm-risk for coronary-events than healthy people. With increasing gravity and duration of ischemia type-II-patients have an increased event-risk. Reliable statements about prognosis of type-III-patients are very difficult. Therapy of SMI is equivalent to therapy of "loud" ischemia and comprises: 1) treatment of cardiovascular risk-factors (nicotine, arterial hypertension, hyperlipidemia, adiposis), 2) nitrates as effective straight at the coronary stenosis, 3) beta-blockers, which influence the circadian ischemic rhythm, 4) calcium-channel-blockers with especially for nifedipine little effect, 5) thrombocyte-aggregation inhibitors and 6) invasive therapeutical methods (percutaneous transluminal coronary angioplasty [PTCA] and aorto-coronary bypass grafting [ACBG]).
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PMID:[Silent myocardial ischemia. Current concepts of prognosis and therapy]. 176 84

During the past decade, large, placebo-controlled, randomized trials have demonstrated that the incidence of coronary events can be reduced by treating hyperlipidemia. In studies with angiographic end points, marked lowering of total and low-density-lipoprotein cholesterol with comparable increases in high-density-lipoprotein cholesterol retards the progression of coronary atherosclerosis and favors regression. In the Cholesterol-Lowering Atherosclerosis Study (CLAS), such therapy also prevented the appearance and worsening of atherosclerotic lesions in coronary bypass grafts. In the recently reported Familial Atherosclerosis Treatment Study (FATS), in which coronary lesions were measured quantitatively, treatment induced clear regression of coronary atherosclerosis and also markedly decreased coronary events. The beneficial effect on coronary lesions in these studies appears to be proportional to the degree of lipid lowering. In addition, new evidence suggests that aspirin and calcium antagonists might prevent the development of early coronary lesions. The identification and aggressive treatment of patients with high serum cholesterol levels can have a major impact on the development and evolution of coronary atherosclerosis.
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PMID:Regression of coronary atherosclerosis: an achievable goal? Review of results from recent clinical trials. 186 31


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