Title:Pleiotropic Effects of PPARγ Agonist on Hemostatic Activation in Type 2 Diabetes Mellitus
Volume: 11
Issue: 3
Author(s): Patrizia Ferroni, David Della-Morte, Antonello Pileggi, Silvia Riondino, Tatjana Rundek, Camillo Ricordi and Fiorella Guadagni
Affiliation:
Keywords:
Atherosclerosis, type 2 diabetes mellitus, haemostasis, platelet activation, PPARγ, PPARγ agonists, thiazolidinediones.
Abstract: Thiazolidinediones (TZDs) represent a class of peroxisome proliferator-activated receptor (PPAR)γ agonists
widely used as insulin-sensitizers in the treatment of type 2 diabetes mellitus (T2DM). The beneficial effects of hypoglycemic
drugs, including TZDs, on the hemostatic abnormalities associated to T2DM have been formerly related to improved
metabolic control, rather than to direct effects. However, in recent years the pleiotropic effects of PPARγ agonists
on hemostatic function have become evident. In particular, the role of platelets as a pivotal player in diabetes complications
by stimulating and sustaining inflammation has been lately acknowledged. Upon activation platelets synthesize and
release many bioactive substances such as thromboxane A2 (TXA2) or pro-inflammatory mediators including CD40 ligand
(CD40L) that exert autocrine and paracrine activation processes in vascular inflammation leading to cardiovascular
disease (CVD). Although PPARγ is a nuclear hormone receptor, anucleate platelets also highly express this receptor and
treatment with synthetic PPARγ ligands dampens the release of soluble(s)CD40L and TXA2 in thrombin-activated platelets.
Moreover, PPARγ through Sirtuin1 pathway has been implicated in modulating inflammatory and atherosclerotic
processes in patients with T2DM. Therefore, in T2DM, where platelet activation contributes to the pathogenesis of CVD,
TZDs may have an enhanced therapeutic role, despite some potentially serious adverse side effects. This review will discuss
the pleiotropic effects of PPARγ treatment on the hemostatic abnormalities associated with T2DM, with particular
focus on platelet activation.
