Pleiotropic Effects of Statins on the Cardiovascular System

Adam Oesterle, Ulrich Laufs, James K. Liao

Research output: Contribution to journalReview article

234 Scopus citations

Abstract

The statins have been used for 30 years to prevent coronary artery disease and stroke. Their primary mechanism of action is the lowering of serum cholesterol through inhibiting hepatic cholesterol biosynthesis thereby upregulating the hepatic low-density lipoprotein (LDL) receptors and increasing the clearance of LDL-cholesterol. Statins may exert cardiovascular protective effects that are independent of LDL-cholesterol lowering called pleiotropic effects. Because statins inhibit the production of isoprenoid intermediates in the cholesterol biosynthetic pathway, the post-translational prenylation of small GTP-binding proteins such as Rho and Rac, and their downstream effectors such as Rho kinase and nicotinamide adenine dinucleotide phosphate oxidases are also inhibited. In cell culture and animal studies, these effects alter the expression of endothelial nitric oxide synthase, the stability of atherosclerotic plaques, the production of proinflammatory cytokines and reactive oxygen species, the reactivity of platelets, and the development of cardiac hypertrophy and fibrosis. The relative contributions of statin pleiotropy to clinical outcomes, however, remain a matter of debate and are hard to quantify because the degree of isoprenoid inhibition by statins correlates to some extent with the amount of LDL-cholesterol reduction. This review examines some of the currently proposed molecular mechanisms for statin pleiotropy and discusses whether they could have any clinical relevance in cardiovascular disease.

Original languageEnglish (US)
Pages (from-to)229-243
Number of pages15
JournalCirculation research
Volume120
Issue number1
DOIs
StatePublished - Jan 6 2017
Externally publishedYes

Keywords

  • cardiovascular diseases
  • cholesterol, LDL
  • hydroxymethylglutaryl-CoA reductase inhibitors
  • rho-associated kinases
  • vascular diseases

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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