Interplay between statins and PPARs in improving cardiovascular outcomes: a double-edged sword?

Statins are best-selling medications in the management of high cholesterol and associated cardiovascular complications. They inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA)-reductase in order to prevent disproportionate cholesterol synthesis. Statins slow the progression of atherosclerosis, prevent the secondary cardiovascular events and improve the cardiovascular outcomes in patients with elevated cholesterol levels. The underlying mechanisms pertaining to the cardioprotective role of statins are linked with numerous pleiotropic actions including inhibition of inflammatory events and improvement of endothelial function, besides an effective cholesterol-lowering ability. Intriguingly, recent studies suggest possible interplay between statins and nuclear transcription factors like PPARs, which should also be taken into consideration while analysing the potential of statins in the management of cardiovascular complications. It could be suggested that statins have two major roles: (i) a well-established cholesterol-lowering effect through inhibition of HMG-CoA-reductase; (ii) a newly explored PPAR-activating property, which could mediate most of cardiovascular protective pleiotropic effects of statins including anti-inflammatory, antioxidant and anti-fibrotic properties. The present review addressed the underlying principles pertaining to the modulatory role of statins on PPARs.