Statins are widely established as an important class of medications for primary and secondary prevention
of cardiovascular disease. In addition to their lipid-lowering effects, mounting evidence suggests that statins
exhibit non-lipid-lowering mediated effects in the cardiovascular system. These so called “pleiotropic” effects are
partly due to antioxidant properties of statins. These are mediated by inhibition of the mevalonate pathway, which
interferes with small GTP-ase protein prenylation. This, in turn, leads to anti-oxidant effects of statins via a plethora
of mechanisms. Statins prevent the activation of the pro-oxidant enzyme NADPH-oxidase by interfering with
Rac1 activation and translocation to the membrane, as well as reducing expression of crucial subunits of
NADPH-oxidase. Statins also enhance the expression, enzymatic activity and coupling of endothelial nitric oxide
synthase (eNOS), through mevalonate-dependent effects. The net result is a restoration of the redox balance in the
cardiovascular system, with subsequent anti-atherosclerotic and cardioprotective effects. While the evidence from
basic science studies and animal models is strong, more clinical trials are required to establish the relevance of
these pleiotropic effects to human cardiovascular disease and potentially lead to expanded indications for statin
treatment or alternative therapeutic strategies.
Keywords: statins, pleiotropic effects, oxidative stress, NADPH-oxidases, eNOS, cardiovascular disease.
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