Pleiotropic Effects of Statins on the Cardiovascular System

By A. Oesterle, Ulrich Laufs, J. Liao. Circulation Research, 2017

1,071 citations recorded by the source corpus.

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.

Subfields: Immunology, Radiology, Nuclear Medicine and Imaging, Surgery

View Paper: https://www.semanticscholar.org/paper/a6f953b7ad2110e4c1c93c3e33f8539676113484

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. Lina Badimon
2. Alberico L. Catapano
3. Rhian M. Touyz

In Radiology, Nuclear Medicine and Imaging

1. Marja-Riitta Taskinen
2. I. Graham
3. Ulrich Laufs

In Surgery

1. I. Graham
2. Marja-Riitta Taskinen
3. Alberico L. Catapano
4. Ulrich Laufs

Citations in the corpus

• Endothelial Dysfunction in Atherosclerotic Cardiovascular Diseases and Beyond: From Mechanism to Pharmacotherapies (2021, background): “Statins,pharmacological inhibitorsofhydroxymethylglutarylcoenzymeA reductase, are first-line pharmaceutical agents to treat hypercholesterolemia and CVD. Statins have both lipid-lowering effects and additional cholesterolindependent or pleiotropic effects (Oesterle et al., 2017).”
• 2019 ESC/EAS guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk. (2019, background): “Although reduction of LDL-C levels is the major effect of statins, a number of other, potentially important effects have been suggested (pleiotropic effects of statins).(204,205) Among such effects that are potentially relevant for the prevention of CVD are the antiinflammatory and antioxidant effec”