Pleiotropic effects of PPARγ agonist on hemostatic activation in type 2 diabetes mellitus

Patrizia Ferroni, David Della Morte, Antonello Pileggi, Silvia Riondino, Tatjana Rundek, Camillo Ricordi, Fiorella Guadagni

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)338-351
Number of pages14
JournalCurrent Vascular Pharmacology
Volume11
Issue number3
DOIs
StatePublished - Jun 11 2013

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Peroxisome Proliferator-Activated Receptors
Hemostatics
Type 2 Diabetes Mellitus
Thiazolidinediones
Platelet Activation
CD40 Ligand
Thromboxane A2
Blood Platelets
Cardiovascular Diseases
Inflammation
Diabetes Complications
Therapeutics
Cytoplasmic and Nuclear Receptors
Hypoglycemic Agents
Thrombin
Blood Vessels
Insulin
Ligands

Keywords

  • Atherosclerosis
  • Haemostasis
  • Platelet activation
  • PPARγ
  • PPARγ agonists
  • Thiazolidinediones
  • Type 2 diabetes mellitus

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology

Cite this

Pleiotropic effects of PPARγ agonist on hemostatic activation in type 2 diabetes mellitus. / Ferroni, Patrizia; Della Morte, David; Pileggi, Antonello; Riondino, Silvia; Rundek, Tatjana; Ricordi, Camillo; Guadagni, Fiorella.

In: Current Vascular Pharmacology, Vol. 11, No. 3, 11.06.2013, p. 338-351.

Research output: Contribution to journalArticle

Ferroni, Patrizia ; Della Morte, David ; Pileggi, Antonello ; Riondino, Silvia ; Rundek, Tatjana ; Ricordi, Camillo ; Guadagni, Fiorella. / Pleiotropic effects of PPARγ agonist on hemostatic activation in type 2 diabetes mellitus. In: Current Vascular Pharmacology. 2013 ; Vol. 11, No. 3. pp. 338-351.
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