Inhibits hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase
REVIEW Rosuvastatin is a competitive inhibitor of HMG-CoA reductase. HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonate, an early rate-limiting step in cholesterol biosynthesis. Rosuvastatin acts primarily in the liver. Decreased hepatic cholesterol concentrations stimulate the upregulation of hepatic low density lipoprotein (LDL) receptors which increases hepatic uptake of LDL. Rosuvastatin also inhibits hepatic synthesis of very low density lipoprotein (VLDL). The overall effect is a decrease in plasma LDL and VLDL. In vitro and in vivo animal studies also demonstrate that rosuvastatin exerts vasculoprotective effects independent of its lipid-lowering properties. Rosuvastatin exerts an anti-inflammatory effect on rat mesenteric microvascular endothelium by attenuating leukocyte rolling, adherence and transmigration. The drug also modulates nitric oxide synthase (NOS) expression and reduces ischemic-reperfusion injuries in rat hearts. Rosuvastatin increases the bioavailability of nitric oxide by upregulating NOS and by increasing the stability of NOS through post-transcriptional polyadenylation. It is unclear as to how rosuvastatin brings about these effects though they may be due to decreased concentrations of mevalonic acid.
REFERENCES
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Di Napoli P, Taccardi AA, Grilli A, De Lutiis MA, Barsotti A, Felaco M, De Caterina R: Chronic treatment with rosuvastatin modulates nitric oxide synthase expression and reduces ischemia-reperfusion injury in rat hearts. Cardiovasc Res. 2005 Jun 1;66(3):462-71.
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Everett BM, Glynn RJ, MacFadyen JG, Ridker PM: Rosuvastatin in the prevention of stroke among men and women with elevated levels of C-reactive protein: justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER). Circulation. 2010 Jan 5;121(1):143-50.
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Jones SP, Gibson MF, Rimmer DM 3rd, Gibson TM, Sharp BR, Lefer DJ: Direct vascular and cardioprotective effects of rosuvastatin, a new HMG-CoA reductase inhibitor. J Am Coll Cardiol. 2002 Sep 18;40(6):1172-8.
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Jones PH, Davidson MH, Stein EA, Bays HE, McKenney JM, Miller E, Cain VA, Blasetto JW: Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial). Am J Cardiol. 2003 Jul 15;92(2):152-60.
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