Telomere/Telomerase system: a new target of statins pleiotropic effect?
Statins are well established drugs for primary and secondary prevention of coronary artery disease (CAD). Despite the well-known ability of statins to lower cholesterol, it is now clear that clinical benefits are also substantially higher than expected and several clinical trials, like JUPITER (Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin trial) have indicated that such clinical effects are independent of cholesterol reduction. These cholesterol-independent actions have been named "pleiotropic effects" and include: anti-oxidation and anti-inflammatory effects, modulation of immune activation, stabilization of atherosclerotic plaque, decreased platelet activation, inhibition of cardiac hypertrophy, reduction of cytokine-mediated vascular smooth muscle cell (VSMC) proliferation and improvement of endothelial function. Recently, additional pleiotropic effects of statins on "cellular senescence" have been seen in different cell types, including endothelial progenitor cells (EPC), endothelial cells (EC), VSMC and chondrocytes. At the molecular level, the effect of statins on cellular senescence could be mediated by their interaction with the telomere/telomerase system. Recent evidence suggests that the anti-aging effects of statins are linked to their ability to inhibit telomere shortening by reducing either directly and indirectly oxidative telomeric DNA damage, as well as by a telomere capping proteins dependent mechanism. In this review, we discuss the pleiotropic effects of statins, focusing on the telomere/telomerase system. We will also present our current findings regarding leukocyte telomere length in very old people with myocardial infarction on statin therapy.
Cardiology Unit, I.N.R.C.A.Hospital, Via della Montagnola, Ancona, Italy.
Fabiola
F
Olivieri
Ilaria
I
Mazzanti
Angela M
AM
Abbatecola
Rina
R
Recchioni
Fiorella
F
Marcheselli
Antonio D
AD
Procopio
Roberto
R
Antonicelli
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D016922:Cellular Senescence / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D019098:Telomerase / Q000187:drug effects* / Q000378:metabolism; D016615:Telomere / Q000187:drug effects* / Q000378:metabolism; D059506:Telomere Shortening / Q000187:drug effects
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019098:Telomerase