title: Pleiotropic effects of statins.
abstract: Statins or 3-hydroxy-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors not only prevents the synthesis of cholesterol biosynthesis but also inhibits the synthesis of essential isoprenoid intermediates such as farnesyl pyrophosphate, geranylgeranyl pyrophosphate, isopentanyl adenosine, dolichols and polyisoprenoid side chains of ubiquinone, heme A, and nuclear lamins. These isoprenoid intermediates are required for activation of various intracellular/signaling proteins- small guanosine triphosphate bound protein Ras and Ras-like proteins like Rho, Rab, Rac, Ral, or Rap which plays an indispensible role in multiple cellular processes. Reduction of circulating isoprenoids intermediates as a result of HMG CoA reductase inhibition by statins prevents activation of these signalling proteins. Hence, the multiple effects of statins such as antiinflammatory effects, antioxidant effects, antiproliferative and immunomodulatory effects, plaque stability, normalization of sympathetic outflow, and prevention of platelet aggregation are due to reduction of circulating isoprenoids and hence inactivation of signalling proteins. These multiple lipid-independent effects of statins termed as statin pleiotropy would potentially open floodgates for research in multiple treatment domains catching attentions of researchers and clinician across the globe.
authors.affiliation: Department of Cardiology, Yashoda Hospital, Secunderabad, India.
authors.forename: Narasaraju
authors.initials: N
authors.lastname: Kavalipati
authors.affiliation: Department of Cardiology, Life Care Institute, Ahmedabad, India.
authors.forename: Jay
authors.initials: J
authors.lastname: Shah
authors.affiliation: Department of Endocrinology, St. John's Medical College, Bangalore, India.
authors.forename: Ananthraman
authors.initials: A
authors.lastname: Ramakrishan
authors.affiliation: Cardiovascular Division, Medical Affairs, AstraZeneca, Bangalore, Karnataka, India.
authors.forename: Hardik
authors.initials: H
authors.lastname: Vasnawala
keywords: Coronary artery disease; pleiotropic effects; rosuvastatin; statins