Atorvastatin increases expression of low-density lipoprotein receptor mRNA in human circulating mononuclear cells

Clinical and Experimental Pharmacology & Physiology
Anothai PocathikornCyril D S Mamotte

Abstract

1. 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) inhibitors, or statins, are commonly used to lower plasma cholesterol levels. HMGCR and the low-density lipoprotein (LDL) receptor (LDLR) are of central importance to cholesterol homeostasis and yet there is a paucity of data on the effect of statins on the regulation of the LDLR and HMGCR in humans. 2. In the present study, we examined the effect of atorvastatin on the expression of HMGCR, LDLR and LDLR-related protein (LRP) mRNA in circulating mononuclear cells. Twelve human volunteers were treated with atorvastatin, 20 mg/day for 4 weeks. 3. Atorvastatin decreased plasma total and LDL-cholesterol by 29% (P < 0.0001) and 41% (P < 0.001), respectively, and increased LDLR mRNA abundance, in absolute terms, by 35% (P < 0.001) and 31% (P < 0.0001) and 37% (P = 0.01) relative to reference GAPDH and beta-actin mRNA, respectively. In contrast, atorvastatin had no significant effect on LRP or HMGCR mRNA levels. 4. The increase in LDLR mRNA in circulating mononuclear cells agrees with the few human studies conducted, as well as with in vitro and animal studies, whereas the unchanged HMGCR mRNA is consistent with the hepatic specificity of atorvastatin. The present study firmly...Continue Reading

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Citations

Feb 9, 2012·Oncogene·J W Clendening, L Z Penn
Jul 5, 2011·Clinical and Experimental Pharmacology & Physiology·Chun-Juan WangYong-Jun Wang
Dec 3, 2010·Journal of Lipid Research·André J TremblayPatrick Couture
Feb 8, 2014·Canadian Journal of Physiology and Pharmacology·Dion R BrocksAyman O S El-Kadi
Oct 17, 2014·Science Translational Medicine·Keith R WalleyJohn H Boyd
Aug 8, 2015·American Journal of Respiratory and Critical Care Medicine·Keith R WalleyJohn H Boyd
Mar 26, 2011·European Journal of Clinical Investigation·Vicenta Llorente-CortesLina Badimon
Oct 21, 2016·Microbes and Infection·Dazhi ZhaoJyothi F Nagajyothi
Jan 21, 2020·Expert Opinion on Pharmacotherapy·Jinhao HuangRongcai Jiang
Apr 18, 2020·Molecular Therapy. Methods & Clinical Development·Ying GongWilfred T V Germeraad

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