Pioglitazone and Endothelial Dysfunction: Pleiotropic Effects and Possible Therapeutic Implications

The vascular endothelium has a central role in the modulation of vascular tone with associated antioxidant, anti-inflammatory, pro-fibrinolytic, anti-adhesive, and anticoagulant effects. This is primarily accomplished by the timely release of endothelial autacoids. On the other hand, endothelial dysfunction (ED) pro-voked by insulin resistance has been linked with reduced nitric oxide bioavailability, increased production of reactive oxygen species, and alterations of endothelial regeneration. Pioglitazone is classified as an insulin-sensitizing, anti-hyperglycemic agent. The mechanism of action associated with pio-glitazone includes the activation of peroxisome proliferator-activated receptor-gamma with stable improvement in glycemic control in diabetic patients. Today, it is known that apart from the beneficial effects on glucose homeostasis, pioglitazone exerts several pleiotropic effects, including the improvement of ED. Thus, the aim of this article was to summarize the current knowledge related to signaling mechanisms of the pioglitazone-induced improvement or reversal of ED. The relevant clinical studies and possible therapeutic implications connected to pioglitazone-related action on the endothelium were analyzed too.