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)

Lovastatin was administered to six hypercholesterolaemic patients (mean plasma cholesterol 450 mg dl-1). Plasma lipoproteins (VLDL, LDL, and HDL) were separated before and following 7 and 12 weeks treatment with lovastatin. Fluidity was quantified by fluorescence polarization measurements using 1,6-diphenyl 1,3,5 hexatriene (DPH) as the fluorescent probe. Lovastatin treatment resulted in a significant reduction of total plasma cholesterol, LDL cholesterol and VLDL cholesterol (-41%, -44%, -68%, respectively). Fluidity measurements showed significant (p < 0.01) increase in LDL fluidity by 11% and 21% after 7 and 12 weeks of lovastatin treatment, whereas, VLDL fluidity was increased by 27% after 12 weeks of therapy. HDL fluidity was not altered. These alterations in the fluidity of the atherogenic lipoproteins (LDL and VLDL) in hypercholesterolaemic patients may prove to be of significance in reducing the risk of atherosclerosis.
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PMID:Effect of lovastatin on lipoprotein fluidity in patients with hypercholesterolaemia. 145 61

Restenosis, the major limitation of balloon angioplasty, is the result of intimal hyperplasia after the procedure. Lovastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) inhibitor, may influence intimal hyperplasia by lowering serum cholesterol and by blocking deoxyribonucleic acid (DNA) synthesis. To determine whether lovastatin reduces intimal hyperplasia, a prospective, randomized blinded study was performed in 60 atherosclerotic New Zealand White male rabbits. Atherosclerosis was produced by air desiccation injury followed by a 28 day diet of 2% cholesterol and 6% peanut oil that was terminated before balloon angioplasty was performed. Angioplasty could not be performed in 14 rabbits with bilateral femoral artery occlusion, and in one rabbit the procedure was a technical failure. Forty-five rabbits underwent balloon angioplasty performed with use of a 2.5-mm balloon inflated to 10 atm for three 1 min dilations at 1 min intervals. Seven rabbits died during the procedure. Thirty-eight rabbits were randomized to either a lovastatin group (6 mg/kg body weight per day) or a control group. Angioplasty was performed on all patent vessels (n = 54); the procedure was bilateral in 16 rabbits and unilateral in 22. Fifteen lovastatin-treated and 15 control rabbits survived 39 days after angioplasty and were then killed. Angiograms, obtained before and 10 min and 39 days after balloon angioplasty, were read with use of electronic calipers by two observers who had no knowledge of treatment data. After the rabbits were killed, vessels were pressure perfused using a standardized protocol to maintain in vivo dimensions for blinded quantitative histologic analysis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of lovastatin on intimal hyperplasia after balloon angioplasty: a study in an atherosclerotic hypercholesterolemic rabbit. 182 71

Epidemiological observations, experimental and clinical researches have laid special stress on the importance of hypercholesterolemia in the natural development of the atherosclerotic disease and its cardiovascular complications. Primary and secondary trials have demonstrated the benefits of cholesterol-lowering therapy to modify the evolution of atherosclerotic disease. In particular, it was observed a significant reduction of incidence and mortality due to coronary heart disease, that is the most common complication of atherosclerosis. At the present time, we have a new class of cholesterol-lowering drugs which is able to inhibit the 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase, the enzyme limiting the endogenous pathway of cholesterol synthesis. The HMGCoA reductase inhibitors, according to the chemical structure, can be divided into two groups. The first includes inactive lactone prodrugs, as Lovastatin and Simvastatin, that are enzymatically hydrolyzed to the corresponding ring-opened active forms in the liver, where the HMGCoA reductase inhibitors must chiefly reduce cholesterol synthesis. To the other group belongs the Pravastatin, a drug that is administered in its active open hydroxyacid form. Several clinical studies seem to demonstrate a greater cholesterol-lowering effect of the active form of Simvastatin, probably because of its more affinity for the HMGCoA reductase enzyme. Up to now, no inhibitor of HMGCoA reductase has showed serious toxic effects in man. The remarkable therapeutic efficacy showed by Simvastatin to reduce the serum concentrations of total and LDL-cholesterol, associated with moderate side-effects, ascribes to this molecule an important role in the therapeutic approach of familial and polygenic hypercholesterolemia.
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PMID:[Hypercholesterolemia: therapeutic approach]. 183 10

HMG-CoA reductase inhibitors have been proven effective in decreasing the plasma cholesterol levels in patients affected with various forms of hypercholesterolemia, familial dysbetalipoproteinemia, familial combined hyperlipidemia and in nephrotic and diabetic dyslipidemia. The purpose of this study was to monitor and evaluate the efficiency and safety of the therapy with simvastatin, an HMG-CoA reductase inhibitor, in a group of patients treated by continuous ambulatory peritoneal dialysis (CAPD) with severe hypercholesterolemia. Monitoring of the changes occurring in the various lipids and apolipoproteins in these patients included the measurements of the plasma lipids and apolipoproteins A-I, A-II, B, C-II, A-IV and Lp(a). Lipoproteins were separated by gel filtration, on a Superose 6HR column, before and after 24 weeks of treatment. The patterns were compared to those observed in a group of primary hyperlipidemic patients treated with Lovastatin, a compound of the same class. The drug was well tolerated by the CAPD patients and no adverse reaction was observed. In addition to the decrease of the total and LDL cholesterol, similar to that reported in other groups of patients, we further observed a decrease of the apo E concentration in both the CAPD and the hyperlipidemic patients. This decrease was especially pronounced in the HDLE fraction and could involve an upregulation of the apo B-E and/or apo E receptor. These results should provide information about the mechanism of action of this drug in patients with end-stage renal disease.
Atherosclerosis 1991 Feb
PMID:Effect of simvastatin treatment on the dyslipoproteinemia in CAPD patients. 187 12

Preincubation of rat adrenocortical cells with lovastatin inhibits high density lipoprotein (HDL3) interaction with rat adrenocortical cells in a dose- and time-dependent fashion. Lovastatin causes a decrease in the number of binding sites and a moderate increase in the affinity of HDL binding to cells. Lovastatin also produced a dose- and time-dependent inhibition of cholesterol synthesis in these cells. Dose-dependence, but not time-dependence, of the inhibition of cholesterol synthesis, correlates with that of HDL binding (r = 0.91, P less than 0.004). Incubation of cells with lovastatin for up to 24 h does not change their free or total cholesterol content. The inhibitory effect was apparently not due to a modification of HDL by lovastatin. These results indicate that lovastatin causes a down-regulation of HDL binding sites on cultured rat adrenocortical cells.
Atherosclerosis 1991 Jun
PMID:Effect of lovastatin on the interaction between high density lipoprotein and cultured rat adrenocortical cells. 189 89

The effects of lovastatin therapy on concentrations and compositions of lipoproteins were examined in 14 patients with heterozygous familial hypercholesterolemia. The drug lowered plasma levels of cholesterol in total plasma, very low density + intermediate density lipoproteins (VLDL + IDL) and low density lipoproteins (LDL) by 25%, 41%, and 41%, respectively. Plasma total apo B was decreased by 35%. Three VLDL subfractions--VLDL-1, VLDL-2, and VLDL-3--of progressively higher density were examined. Lovastatin therapy reduced only the heaviest--VLDL-3. Concentrations of VLDL-1 and VLDL-2 were unchanged. Total VLDL-cholesterol/apo B was reduced significantly. Drug therapy also altered the composition of LDL as shown by decreasing the cholesterol/apo B. Finally, lovastatin significantly raised HDL-cholesterol concentrations. This study showed that lovastatin modifies the composition of the major apo B-containing lipoproteins as well as reducing their concentrations.
Atherosclerosis 1990 Oct
PMID:Influence of lovastatin on concentrations and composition of lipoprotein subfractions. 228 90

We examined the relationship between cholesterol synthesis and high affinity low density lipoprotein (LDL) catabolism in freshly isolated mononuclear leukocytes and plasma sterols and apolipoprotein concentrations in three homozygous and one heterozygous subject with sitosterolemia with xanthomatosis and in 12 control subjects. Observations in untreated subjects were compared during therapy with lovastatin or interruption of the enterohepatic circulation of bile acids. Plasma cholesterol, plant sterol, and apolipoprotein B concentrations declined more than 50% in the two homozygous sitosterolemic subjects after ileal bypass surgery. In contrast, plasma cholesterol, plant sterol, and apolipoprotein B concentrations remained constant in a homozygous sitosterolemic subject and declined only 7% in a heterozygous sitosterolemic subject during 20 weeks of lovastatin (40 mg/day) treatment compared to a 28% decrease in similarly treated control subjects. Lovastatin treatment decreased cholesterol synthesis more than 60% but did not increase high affinity catabolism of LDL further in the sitosterolemic cells, compared to a more than 20% rise in control mononuclear leukocytes. Conversely, bile acid malabsorption increased cholesterol synthesis 59%, total hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase activity 13%, and receptor-mediated LDL degradation 41% in control cells, but did not stimulate cholesterol synthesis or microsomal HMG-CoA reductase activity in sitosterolemic mononuclear leukocytes although receptor-mediated LDL catabolism rose an additional 26%. These results demonstrate a greater than expected decrease in plasma sterols and apolipoprotein B concentrations in sitosterolemic subjects after stimulation of bile acid synthesis because of the inability to up-regulate cholesterol production. We suggest that bile acid-sequestering drugs or ileal exclusion surgery may be more effective treatments to mobilize accumulated sterol deposits and prevent atherosclerosis in this disease.
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PMID:Unexpected failure of bile acid malabsorption to stimulate cholesterol synthesis in sitosterolemia with xanthomatosis. Comparison with lovastatin. 231 63

The effect of lovastatin therapy on LDL-receptor activity in fresh monocytes and on the structure and composition of lipoproteins was determined in 9 patients with familial hypercholesterolemia (FH) and 8 patients with non-familial hypercholesterolemia (NFH). Lovastatin reduced LDL-cholesterol levels by 34.8 and 47.5%, respectively, in the 2 groups of patients, and plasma apo B levels by 33.3 and 42.5%. LDL receptor activity in fresh monocytes increased by 53% and 86% respectively. HDL-cholesterol and plasma apo A-I levels increased only in the NFH group, by 10.2 and 7.1%. Lipoproteins were separated by centrifugation on a zonal rotor. Except for the intermediate density lipoprotein (IDL) fraction, no changes were observed in the structure and composition of the various lipoproteins. The investigations thus demonstrated that lovastatin therapy is associated with a measurable and significant increase of LDL-receptor activity in circulating monocytes that may contribute to the lipid lowering action of the drug.
Atherosclerosis 1990 May
PMID:Effects of lovastatin therapy on LDL receptor activity in circulating monocytes and on structure and composition of plasma lipoproteins. 236 Sep 16

Lovastatin was investigated in a single-blind placebo-controlled trial in 150 patients with coronary atherosclerosis confirmed by coronary angiographic studies and those with nonfamilial hyperlipoproteinemia. After 3 months of treatment total cholesterol (TC) level was reduced by 36% (p less than 0.001), LDL cholesterol level by 48% (p less than 0.001), triglycerides level by 19% (p less than 0.001), VLDL cholesterol by 24% (p less than 0.01), whereas the HDL-cholesterol level was increased by 36% (p less than 0.001). Besides, concentration of apolipoprotein A-I increased by 19% (p less than 0.05), apolipoprotein B decreased by 22% (p less than 0.05) and the ratios of LDL cholesterol/HDL cholesterol and TC/HDL cholesterol decreased by 64% and 56%, respectively (p less than 0.001). The side effects of lovastatin were negligible. Thus, lovastatin is a highly effective and well tolerated hypolipidemic drug for the treatment of patients with IHD and hyperlipoproteinemia.
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PMID:[The effectiveness of the hypolipemic preparation lovastatin in patients with ischemic heart disease and hyperlipoproteinemia]. 260 92

Hypercholesterolemia (type II hyperlipidemia) after cardiac transplantation is common and may play a role in the accelerated rate of coronary atherosclerosis seen following the procedure. However, conventional cholesterol-lowering drugs are either ineffective or contraindicated for use in transplant recipients. The presence of type II hyperlipidemia was identified in 11 cardiac transplant recipients during a mean follow-up period of 15 months (range 3 to 41) after transplantation. Lovastatin, at an initial dosage of 20 mg/day, was administered for a period of 1 year. The maximal dosage of lovastatin was 60 mg/day. All patients received maintenance dosages of immunosuppressive agents, including cyclosporine-A, prednisone and, in some instances, azathioprine. Lipid profiles, hepatic transaminases, serum creatinine, creatine kinase and cyclosporine-A serum trough levels were measured quarterly. Total cholesterol decreased by 27% (354 +/- 50 vs 258 +/- 36 mg/dl, p less than 0.01) after 3 months and remained stable thereafter. Similarly, low density lipoprotein cholesterol decreased by 34% (221 +/- 51 vs 146 +/- 40 mg/dl, p less than 0.01) after 3 months and remained constant. Triglycerides, high density lipoprotein, hepatic transaminases, creatinine, creatine kinase and trough cyclosporine-A levels remained stable during the 1-year follow-up period. Lovastatin was uniformly well tolerated in this study group. When given in modest dosages, lovastatin appears to be a safe, effective and well-tolerated therapy for hypercholesterolemia in cardiac transplant recipients.
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PMID:Lovastatin therapy for hypercholesterolemia in cardiac transplant recipients. 267 84


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