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.
Keywords: Atherosclerosis, type 2 diabetes mellitus, haemostasis, platelet activation, PPARγ, PPARγ agonists, thiazolidinediones.
Current Vascular Pharmacology
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.
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Ferroni Patrizia, Della-Morte David, Pileggi Antonello, Riondino Silvia, Rundek Tatjana, Ricordi Camillo and Guadagni Fiorella, Pleiotropic Effects of PPARγ Agonist on Hemostatic Activation in Type 2 Diabetes Mellitus, Current Vascular Pharmacology 2013; 11 (3) . https://dx.doi.org/10.2174/1570161111311030008
DOI https://dx.doi.org/10.2174/1570161111311030008 |
Print ISSN 1570-1611 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6212 |
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