title: Pleiotropic effects of PPARγ agonist on hemostatic activation in type 2 diabetes mellitus.
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.
authors: Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy. patrizia.ferroni@sanraffaele.it
authors: Patrizia
authors: P
authors: Ferroni
authors: David
authors: D
authors: Della-Morte
authors: Antonello
authors: A
authors: Pileggi
authors: Silvia
authors: S
authors: Riondino
authors: Tatjana
authors: T
authors: Rundek
authors: Camillo
authors: C
authors: Ricordi
authors: Fiorella
authors: F
authors: Guadagni
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D006487:Hemostasis / Q000187:drug effects; D020141:Hemostatic Disorders / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000494:pharmacology; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects; D045162:Thiazolidinediones / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones