Elevated plasma levels of asymmetric dimethylarginine (ADMA) have been associated with attenuated endothelium-dependent vasodilation in hypercholesterolemic patients. However, whether lowering of plasma cholesterol concentration by hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) can reduce plasma ADMA levels is still not clear. This study was a multicenter, randomized, double-bl...

BACKGROUND Chlamydia pneumoniae stimulates chronic inflammation in vascular cells. Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) may have an ameliorating effect. We investigated possible mechanisms. METHODS AND RESULTS We infected human macrophages that in coculture spread infection to vascular smooth muscle cells (VSMCs). Cerivastatin (250 nmol/L) reduced VSMC infection by ...

Several prospective clinical studies have indicated that hydroxymethylglutaryl-coenzyme A reductase inhibitors, statins, prevent cardiovascular events in part through their antiinflammatory properties. Because inflammation is positively and negatively regulated by T helper (Th) 1 cells and Th2 cells, respectively, we examined the effects of statins on the Th polarization in vitro and in vivo. H...

We investigated effects of fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, and its major metabolites, M2 and M4, on CuSO4-induced low-density lipoprotein (LDL) oxidation and cholesteryl ester accumulation in mouse peritoneal macrophages. All the test compounds inhibited LDL oxidation, and M2 had the most potent effect comparable to vitamin E. When LDL was pre...

Hydrogen sulfide (H2S) is a crucial co-modulator of cardiovascular, nervous, digestive and excretory systems function. The pleiotropic action of atorvastatin exceeds simple 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibition and involves multiple biological mechanisms. This study assesses the influence of atorvastatin on the H2S tissue concentration in mouse brain, liver, heart...

Immunoprecipitation of native rat liver microsomal 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, phosphorylated by [gamma-32P]ATP in the presence of reductase kinase, revealed a major 97-kDa 32P band which disappeared upon competition with pure unlabeled 53-kDa HMG-CoA reductase. A linear correlation between the expressed/total HMG-CoA reductase activity ratio (E/T) and the fractio...

Soluble 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase, EC 1.1.1.34) from rat liver microsomes has been shown to be inactivated reversibly by cold temperature whereas microsomal enzyme did not show any cold sensitivity. At 0” the soluble enzyme lost 80% of its activity within 30 min and warming at 37” for 20 min restored all the lost activity. Active enzyme preparations did ...

We employed the overexpressed catalytic domains of wild-type Syrian hamster 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase, EC 1.1.1.34) and of mutant enzymes E558Q, H865Q, and D766N to investigate the roles of Glu558, His865, and Asp786 in catalysis. Five reactions were studied: reductive deacylation of HMG-CoA or of mevaldyl-CoA to mevalonate, reduction of mevaldehyde to m...

Emerging data suggest that the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) offer important benefits for the large population of individuals at high risk for coronary heart disease. This population encompasses a sizable portion of individuals who are also at high risk for drug-drug interactions due to their need for multiple medications. In general, statins are...

ML236B is a potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoA reductase) (EC 1.1.1.34), the major regulatory enzyme in cholesterol biosynthesis. This compound inhibits cell growth when present in the culture medium of CHO-K1 cells at a concentration as low as 0.1 pg/ml. Addition of the product of the HMG-CoA reductase reaction, mevalonate, to the culture me...