Disease relevance of lovastatin

• The efficacy of intensive dietary therapy alone or combined with lovastatin in outpatients with hypercholesterolemia [1].
• Rhabdomyolysis in patients receiving lovastatin after cardiac transplantation [2].
• The beneficial effects of lovastatin on plasma lipid levels in patients with NIDDM could decrease the risk of the development of coronary heart disease [3].
• At base line the mean (+/- SD) degree of stenosis, expressed as a percentage of the diameter of the vessel, was 64 +/- 11 percent in the lovastatin group, as compared with 63 +/- 11 percent in the placebo group (P = 0.22) [4].
• Myolysis and acute renal failure in a heart-transplant recipient receiving lovastatin [5].

Psychiatry related information on lovastatin

• PURPOSE: In our initial study of the potential effects of cholesterol-lowering interventions on cognitive functioning, treatment with lovastatin as compared with placebo caused performance decrements on several neuropsychological tests, whereas scores on other tests were unaffected [6].
• Atherogenic risk reduction in patients with dyslipidaemia. comparison between bezafibrate and lovastatin [7].
• These results provide an insight into the mechanism of the beneficial effects of lovastatin in neurodegenerative disorders, particularly Alzheimer's disease [8].
• This open-labeled, multicenter study evaluated the safety of bedtime niacin extended-release/lovastatin when dosed as initial therapy and patient compliance to treatment in various clinical practice settings [9].
• Pravastatin did not differ from placebo regarding any polysomnographic measures, but was associated with worsening in relation to lovastatin in the following parameters: sleep efficiency, entries to wake, percent rapid eye movement sleep, wake time during sleep, and total wake time [10].

High impact information on lovastatin

• Lovastatin for X-linked adrenoleukodystrophy [11].
• Cholesterol lowering with lovastatin significantly improved endothelium-mediated responses in the coronary arteries of patients with atherosclerosis [12].
• In a randomized, double-blind, placebo-controlled trial, we studied coronary endothelial responses in 23 patients randomly assigned to either lovastatin (40 mg twice daily; 11 patients) or placebo (12 patients) plus a lipid-lowering diet (American Heart Association Step 1 diet) [12].
• Despite a 42 percent reduction in the serum level of low-density lipoprotein cholesterol in the lovastatin group, after six months of treatment the amount of stenosis seen in the second angiogram was 46 +/- 20 percent in the placebo group, as compared with 44 +/- 21 percent in the lovastatin group (P = 0.50) [4].
• We now show that treatment of cells with lovastatin, which inhibits modification of small GTP-binding proteins, reduced PIP2 levels and decreased calcium mobilization in response to PDGF and thrombin [13].

Chemical compound and disease context of lovastatin

• Because of the potential for severe myopathy and life-threatening rhabdomyolysis, and given alternative drug combinations for treating hyperlipoproteinemia, the use of lovastatin in combination with gemfibrozil is to be discouraged [14].
• In this study, lovastatin and colestipol hydrochloride together were administered to ten patients with primary moderate hypercholesterolemia [15].
• Plasma mevalonate response in lovastatin-related myopathy [16].
• We examined the effects of HMG-CoA reductase inhibitors, fluvastatin and lovastatin, on human pancreatic cancer cell invasion in vitro and experimental liver metastasis in vivo [17].
• RESULTS: Lovastatin, 10-30 micromol/L, augmented sulindac-induced apoptosis up to 5-fold in 3 colon cancer cell lines [18].

Biological context of lovastatin

• A broad spectrum of Cdk-inhibitory activity associated with a 28-kilodalton protein (p28lck1) was induced in cells treated with the drug lovastatin or upon density-mediated growth arrest and was periodic in the cell cycle, with peak activity in G1 [19].
• OBJECTIVE: To assess the lipid-lowering efficacy, biochemical safety, and effect on growth and sexual development of lovastatin in adolescent boys with HeFH [20].
• Growth and sexual maturation assessed by Tanner staging and testicular volume were not significantly different between the lovastatin and placebo groups at 24 weeks (P = .85) and 48 weeks (P = .33); neither were serum hormone levels or biochemical parameters of nutrition [20].
• Thus, a low dose of lovastatin appears highly effective for treatment of moderate hypercholesterolemia in most postmenopausal women, presumably because it reverses the reduction in LDL receptor activity associated with menopause [21].
• The isoprenoid end product isopentenyl adenine (5 or 50 microM) had little effect on DNA synthesis and cell proliferation in lovastatin-blocked cells [22].

Anatomical context of lovastatin

• Lovastatin, a nonreversible inhibitor of HMG-CoA reductase, induced extensive cytotoxicity that was restricted to drug-resistant P-glycoprotein-expressing neuroblastoma cell lines [23].
• Lovastatin inhibits proliferation of rat mesangial cells [22].
• Inhibition of LPS-mediated activation of NF-kbeta by lovastatin, NaPA, and FPT inhibitor II in astrocytes indicates that the observed inhibition of iNOS expression is mediated via inhibition of NF-kbeta activation [24].
• In addition to iNOS, lovastatin and NaPA also inhibited LPS-induced expression of TNF-alpha, IL-1beta, and IL-6 in rat primary astrocytes, microglia, and macrophages [24].
• Lovastatin was shown to protect the ischemic rabbit myocardium by three different indices of ischemic damage: (a) maintenance of creatine kinase (CK) activity in the ischemic myocardium; (b) reduced loss of free amino-nitrogen containing compounds from the ischemic myocardium; and (c) blunting the rise of plasma CK activity [25].

Associations of lovastatin with other chemical compounds

• INTERVENTION--Patients received a Step II Diet and lovastatin (40 mg daily) plus colestipol (30 g daily), niacin (4 g daily) plus colestipol, or placebo (plus colestipol if LDL-C > 90th percentile) for 2.5 years [26].
• A randomized, crossover design consisted of two drug phases (lovastatin and gemfibrozil) alternating with placebo [27].
• Treatment with lovastatin (mevinolin) one year after transplantation produced a marked improvement in the patient's lipoprotein profile [28].
• Lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, blocks the formation of mevalonate and its metabolites, and has been shown to inhibit proliferation of several cell types [22].
• Finally, the mGSH depletion induced by acetaldehyde sensitized HepG2 cells to tumor necrosis factor (TNF)-alpha-induced apoptosis that was prevented by cyclosporin A, GSH ethyl ester, and lovastatin [29].

Gene context of lovastatin

• Further analysis demonstrated that Cx26 is a cell-cycle regulated gene expressed at a moderate level during G1 and S, and strongly up-regulated in late S and G2, as shown with lovastatin-synchronized NMECs [30].
• Our study suggests that lovastatin, alone or in combination with a MEK1 inhibitor, may represent a new and immediately available therapeutic approach to combat tumors with activated ERK1/2, such as AML [31].
• We show that p38 and c-Jun NH2-terminal kinase/stress-activated kinase MAPK pathways are not altered during lovastatin-induced apoptosis [31].
• Up-regulation of LDL receptors by lovastatin treatment of normal human foreskin fibroblasts (FSF cells) resulted in an increase in LPL-induced VLDL binding and catabolism to a level that was 10-15-fold greater than in LDL receptor-negative fibroblasts, despite similar LRP activity in both cell lines [32].
• By using p21 promoter deletion constructs, the lovastatin-responsive element was mapped to a region between -93 and -64 relative to the transcription start site [33].

Analytical, diagnostic and therapeutic context of lovastatin

• Treatment with high-dose lovastatin initiated before coronary angioplasty does not prevent or delay the process of restenosis in the first six months after the procedure [4].
• The ratio of LDL to HDL cholesterol and the level of total triglycerides were reduced by lovastatin (P < 0.001), but not by the low-fat diet [1].
• In the second part, hypercholesterolemic women participated in a placed-controlled, randomized, double-blind study using lovastatin as the therapeutic agent [21].
• INTERVENTION: Lovastatin, starting at 10 mg/d, with a forced titration at 8 and 16 weeks to 20 and 40 mg/d, respectively, or placebo [20].
• Thus, the combination of liver transplantation and lovastatin restored total and LDL cholesterol levels to normal in this patient with homozygous familial hypercholesterolemia [28].

References