The effects of statins with a high hepatoselectivity rank on the extra-hepatic tissues; new functions for statins

Abstract Statins, as the most common treatment for hyperlipidemia, have effects beyond their lipid-lowering role which are known as pleiotropic effects. These effects are mainly due to the inhibition the isoprenoids synthesis and consequently the blocking prenylation of proteins involved in the cellular signaling pathways regulating various cellular processes including cell development, growth, and apoptosis. Statins target cholesterol synthesis in the liver as the major source of cholesterol in the body and so reduce whole-body cholesterol. The reduced level of cholesterol probably forces other organs to an adaptive homeostatic reaction to increase their cholesterol synthesis capacity, but this only happens when statins have unremarkable access to the extra-hepatic tissues. In order to reduce the adverse effects of statin on the skeletal muscle, most recent efforts have been towards formulating new statins with the highest level of hepatoselectivity rank and the least level of access to the extra-hepatic tissues; however, the inaccessibility of statins for the extra-hepatic tissues may induce several biological reactions. In this review, we aim to consider the effects of statins on the extra-hepatic tissues when statins have unremarkable access for these tissues.