Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Large (Sf greater than 100) and small (Sf 100-20) very low density lipoprotein (VLDL) particles were isolated by density gradient ultracentrifugation and characterized chemically in 8 patients with primary hypertriglyceridemia before and after 6 weeks treatment with 4 grammes daily of nicotinic acid (NA). Concomitant changes in high density lipoprotein (HDL) subclass distribution were determined by gradient gel electrophoresis. Small VLDL was subjected to lipolysis in vitro by incubation with bovine lipoprotein lipase before and after NA, and the change in the lipolytic end-product isolated in the low density lipoprotein (LDL) fraction was investigated. Reductions were achieved in the plasma levels of triglycerides, free and esterified cholesterol, phospholipids and proteins in the two VLDL subfractions. In all, the composition of both large and small VLDL particles changed towards potentially less atherogenic particles that were poorer in cholesteryl esters. The HDL cholesterol concentration increased and the HDL protein distribution on gradient gel electrophoresis changed towards larger particles. The mechanism behind the change in cholesterol distribution between VLDL and HDL after NA treatment is unclear, but it could possibly relate to decreased lipid transfer activity. NA reduced the content of apolipoprotein B in both VLDL subclasses and did not decrease the calculated particle size or the number of triglyceride molecules per particle, indicating a reduction of VLDL particle number rather than of particle size. The LDL density fraction isolated after lipolysis in vitro of small VLDL contained less total cholesterol and phospholipids and had a density profile more similar to native LDL after the patients had been treated with NA.
Atherosclerosis 1990 Oct
PMID:Normalisation of the composition of very low density lipoprotein in hypertriglyceridemia by nicotinic acid. 228

Modifications in plasma low and high density lipoprotein (LDL and HDL) subfraction distribution, as well as the regulation of cellular LDL metabolism by hypertriglyceridemic LDL were tested before and after treatment with acipimox, a nicotinic acid derivative, in 11 type IV hyperlipidemic patients. Large, less dense LDL particles were found in plasma after acipimox treatment, reflecting compositional changes, characterized by a 25.4% increase in cholesteryl ester content and by a 46.2% reduction of triglycerides in LDL. HDL subfractions were only slightly modified, with an increase of dense, cholesteryl ester-enriched and triglyceride poor HDL3 particles. The LDL (B,E) receptor activity in humans skin fibroblasts of LDL isolated before and after treatment was also evaluated. Hypertriglyceridemic LDL proved rather inefficient in regulating receptor activity with a close to 30% reduction vs. normal LDL in the capacity to inhibit receptor-mediated uptake and degradation of 125I-LDL. Such abnormality was fully corrected after acipimox. The reported findings indicate that acipimox treatment in type IV patients, in spite of a relatively modest plasma triglyceride reduction, can markedly modify LDL distribution and composition, normalizing the defective interaction of hypertriglyceridemic LDL with the LDL (B,E) receptor.
Atherosclerosis 1990 Feb
PMID:Lipoprotein changes and increased affinity of LDL for their receptors after acipimox treatment in hypertriglyceridemia. 230 5

The development of femoral atheroma after 1 year of treatment with diet and nicotinic acid plus fenofibrate was studied in 45 asymptomatic, hyperlipidaemic, middle-aged male subjects in a non-randomized controlled study. The median serum very low density lipoprotein (VLDL) cholesterol concentration and the low density lipoprotein (LDL) cholesterol concentration were lowered by 67% and 36%, respectively, in the treatment group. The median serum high density lipoprotein (HDL) cholesterol concentration was increased by 23%. Femoral atheroma was estimated by overall atherosclerosis score (OAS). Changes in femoral atherosclerosis were estimated by intrapair comparison of angiograms. Progression was found in 24% and 40% in the treatment and control groups, respectively. Regression occurred in 29% and 0%, respectively. The OAS decrease correlated with reductions in VLDL cholesterol and systolic blood pressure.
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PMID:The effect of serum lipid regulation on the development of femoral atherosclerosis in hyperlipidaemia: a non-randomized controlled study. 235 25

Hyperlipidemia is usually present in patients with the nephrotic syndrome. The most common lipid abnormality is hypercholesterolemia, although as the disorder progresses, hypertriglyceridemia may develop. Elevated plasma lipids have two potential vascular consequences, namely, atherosclerosis and progression of renal failure. Neither of these complications has been proven with certainty, but there is growing evidence to indicate that both may be long-term consequences of the nephrotic syndrome. Therefore, effective therapy of hyperlipidemia, particularly elevated cholesterol levels, is needed as a protection against these complications. Since nephrotic hypercholesterolemia frequently is severe, dietary therapy, although a valuable adjunct, will not normalize cholesterol levels in most nephrotic patients. Thus, if effective serum cholesterol lowering is to be achieved, drug therapy will be required. Bile acid-binding resins have been shown to lower cholesterol levels in nephrotic patients, but the decline in cholesterol concentrations is usually insufficient to produce a marked reduction in coronary risk. Nicotinic acid theoretically should be useful for treatment of nephrotic hyperlipidemia, but it has not been adequately tested. The new drugs that inhibit cholesterol synthesis, e.g., lovastatin, appear to be highly promising for treating elevations of both serum cholesterol and triglycerides in the nephrotic syndrome. However, testing of these drugs in this condition has been limited, and the possibility of significant side effects in an appreciable portion of patients has not been ruled out. Of particular concern is the development of severe myopathy that can produce myoglobinuria and acute renal failure. This side effect is relatively rare in patients without the nephrotic syndrome, but its prevalence in the latter condition has not been determined. The fibric acids will lower triglyceride levels in nephrotic patients, but they are not effective in lowering cholesterol levels; consequently, they probably have little role in the treatment of nephrotic hypercholesterolemia. Finally, the drug probucol will lower cholesterol levels in nephrotic patients, although not to desirable levels; still, probucol could prove useful in combination with other cholesterol-lowering drugs.
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PMID:Rationale and management of hyperlipidemia of the nephrotic syndrome. 248 42

Patients with heterozygous familial hypercholesterolemia (FH) constitute a unique population at high risk for the premature development of coronary artery disease (CAD) and in whom long-term hypocholesterolemic therapy to reduce elevated levels of low density lipoprotein (LDL) cholesterol is most clearly indicated. Optimal therapy invariably requires diet regulation plus hypolipidemic drug therapy. When used as single agents, the bile-acid sequestrants, cholestyramine and colestipol, lower LDL cholesterol concentrations by 20% to 35% in compliant patients, whereas decreases of 20% to 30% can be achieved with nicotinic acid in doses of 3 to 6 g/day. Bezafibrate, fenofibrate, and ciprofibrate have also been shown to lower LDL cholesterol levels by 20% to 30%, and these drugs are more effective than gemfibrozil and clofibrate. Probucol, neomycin, and D-thyroxine reduce LDL cholesterol concentrations by 10% to 15% in single-drug use. Clinical trials with a new class of drugs that inhibit the rate-limiting enzyme in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, and that includes lovastatin, simvastatin, and pravastatin indicate that these drugs lower LDL cholesterol concentrations by 30% to 50% in patients with heterozygous FH. Combined drug therapy with a bile-acid sequestrant and nicotinic acid lowers LDL cholesterol by 40% to 55%, whereas fenofibrate, bezafibrate, or probucol plus a bile-acid sequestrant results in reductions varying from 25% to 50%. The combinations of an HMG CoA reductase inhibitor with either a bile-acid sequestrant or nicotinic acid appears to be the most promising, and these regimens reduce LDL cholesterol levels by 45% to 60%. With appropriate use, the currently available hypocholesterolemic drugs have the potential to markedly change the natural history of premature atherosclerosis that occurs in untreated patients with FH.
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PMID:Treatment of heterozygous familial hypercholesterolemia with lipid-lowering drugs. 249 89

The results of the World Health Organization Cooperative Trial, the Coronary Drug Project, the Coronary Primary Prevention Trial and the Helsinki Heart Study indicate that clinical expression of coronary artery disease can be delayed with pharmacologic modification of plasma lipoproteins. Change in coronary artery disease can be semiquantitated by repeat arteriograms. Three randomized clinical trials indicate that rate of progression of atherosclerosis, as defined by arteriography, can be reduced, and existing lumen obstruction decreased. Tendon xanthomas occur in hypercholesterolemia, and reduction in xanthoma size with drug therapy suggests an improved atherosclerotic disease state. The clinician has a variety of pharmacologic therapies available. The role of bile acid-binding resins, fibric acid derivatives, hydroxymethylglutaryl coenzyme A reductase inhibitors, nicotinic acid and antioxidants is each unique. Understanding the role of lipoproteins in atherosclerosis will help in selecting the most appropriate therapy for each individual patient. Medications not designed for their lipoprotein effects can significantly alter lipoproteins. Medications, such as nonselective beta blockers, can alter low-density lipoprotein (LDL) subclass distribution with no change in LDL cholesterol content. Such changes may eradicate part of the beneficial cardiovascular effect of beta blockade therapy. In the future, therapeutic choices may depend in part on lipoprotein abnormalities such as lipoprotein (a), apolipoprotein E isoforms, hyperapobetalipoproteinemia, LDL.
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PMID:Drug therapy and the prevention of atherosclerosis in humans. 267 29

There are indications that treatment of hypercholesterolemia by means of drugs reduce risk of atherosclerosis in patients with increased concentrations of atherogenic lipoproteins. Such therapy should be initiated only after satisfactory exclusion of secondary causes of hyperlipoproteinemia, and should be regarded as an adjunct to appropriate dietary therapy. Drug therapy should be strongly considered in patients with total cholesterol above 8-9 mmol/l on diet therapy only. Drug therapy should be considered at even lower concentrations of cholesterol when coronary heart disease is present and in familial forms of hyperlipidemia when increased risk of atherosclerosis has been documented. In patients with increased plasma concentrations of total cholesterol the drugs of choice are agents which enhance the rate of LDL catabolism (resins) or reduce the rate of LDL synthesis (nicotinic acid). Fibrates should be used when triglycerides and cholesterol are both increased. HMG CoA reductase inhibitors offer considerable promise in the therapy of patients with primary hypercholesterolemia. Probucol may be used in combination with other drugs, particularly when xanthomas are present in patients with familial hypercholesterolemia.
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PMID:[Drug therapy of hypercholesterolemia. Treatment of hypercholesterolemia in adults--a Norwegian therapeutic program 1988]. 270 70

The article analyses the immediate results of preoperative management and treatment of 13 patients with atherosclerosis obliterans of the lower limbs on the basis of drug hypolipidemic therapy and hemosorption on nonspecific sorbents of type CKH. Drug therapy comprised nicotinic acid, its derivatives in a daily dose of up to 2.5 mg, cholestiramine up to 20 g daily, vitamin therapy, and prodectin. Hemosorption was conducted on CKH-2K once in 4 days; 7 patients were given 5 perfusions each, 6 patients--7 perfusions each. Considerable clinical improvement occurred, hemodynamics improved, improvement of lipid metabolism was manifested by decrease of total cholesterol by 22%, triglycerides by 10%, and low density lipoproteins by 43% and increase of high density lipoproteins by 100%. The Cch atherogenicity coefficient decreased by 41%. The expediency of conducting no more than 4 sorptions was revealed and substantiated. Reconstructive vascular operations were performed on the patients. The postoperative period was uneventful. The late-term postoperative period was marked by progressive improvement of rheographic and biochemical values and stable normalization of lipid metabolism.
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PMID:[Preoperative preparation of patients with arteriosclerosis obliterans]. 272 47

The pathogenesis of atherosclerosis is a multifactorial process. A possible anti-atherosclerotic drug should therefore interfere with different targets that are important during the development of an atherosclerotic lesion. Two of the early events are the activated migration and proliferation of arterial smooth muscle cells. Here we investigated in several in vivo and in vitro experiments the effect of two nicotinic acid derivatives L44 and L44-0, on smooth muscle cell migration and proliferation. Balloon catheter de-endothelialization was used as an animal model for intimal lesion formation. Migration was subsequently quantified in vitro using the explant outgrowth technique. Subcultured smooth muscle and endothelial cells were used to test the effect of the drugs on proliferation. Time-lapse video microscopy was applied to differentiate between smooth muscle cell migration and proliferation on the level of individual cells. We showed that L44 and L44-0 are very effective in decreasing smooth muscle cell proliferation and migration. Endothelial cell proliferation, important to re-establish endothelial integrity was, however, not affected.
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PMID:Differential effect of nicotinic acid derivatives on smooth muscle and endothelial cell proliferation. 276 60

High-density lipoprotein (HDL) cholesterol, an independent coronary heart disease (CHD) risk factor, is inversely associated with CHD. Whether interventions to increase concentrations of HDL--particularly the HDL2, HDL3, and apolipoprotein A1 subfractions--will reduce the incidence of CHD in high-risk patients is thus an area of intense speculation. Both nonpharmacologic and pharmacologic regimens will raise HDL concentrations. Nonpharmacologic approaches include habitual high-level aerobic exercise and weight loss--both of these somewhat more effective in men than in women--cessation of cigarette smoking, and changing of dietary habits. A number of drugs have been found to elevate HDL cholesterol. These include the bile acid-binding resin cholestyramine, nicotinic acid, gemfibrozil, phenytoin, exogenous estrogens, and alcohol. Terbutaline has also been reported to raise HDL cholesterol. It is not yet known whether, and to what degree, pharmacologic and nonpharmacologic elevation of HDL cholesterol will retard or reverse the progression of atherosclerosis. Conversely, HDL cholesterol is lowered by a broad variety of drugs, including anabolic--androgenic steroids, exogenous progestins, and probucol, which are used therapeutically to reduce low-density lipoprotein (LDL) cholesterol. Some agents used to treat hypertension also reduce HDL cholesterol, especially thiazide diuretics and the beta blockers, with the possible exception of pindolol. In the antiadrenergic class of antihypertensive agents, reserpine and methyldopa lower HDL cholesterol, but the alpha blocker prazosin does not appear to affect HDL cholesterol. The alpha agonist guanabenz has no effect on HDL cholesterol, and the vasodilator carprazidil has been reported to raise HDL cholesterol. In light of these facts, investigations should be undertaken to determine whether the metabolic effects of antihypertensive agents blunt their beneficial effects on CHD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nonpharmacologic and pharmacologic alteration of high-density lipoprotein cholesterol: therapeutic approaches to prevention of atherosclerosis. 286 87


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