Enhanced Integrin Activation of PLD2-Deficient Platelets Accelerates Inflammation after Myocardial Infarction.

Background: Phospholipase (PL)D1 is crucial for integrin alpha(IIb)beta(3) activation of platelets in arterial thrombosis and TNF-alpha-mediated inflammation and TGF-beta-mediated collagen scar formation after myocardial infarction (MI) in mice. Enzymatic activity of PLD is not responsible for PLD-mediated TNF-alpha signaling and myocardial healing. The impact of PLD2 in ischemia reperfusion injury is unknown. Methods: PLD2-deficient mice underwent myocardial ischemia and reperfusion (I/R). Results: Enhanced integrin alpha(IIb)beta(3) activation of platelets resulted in elevated interleukin (IL)-6 release from endothelial cells in vitro and enhanced IL-6 plasma levels after MI in PLD2-deficient mice. This was accompanied by enhanced migration of inflammatory cells into the infarct border zone and reduced TGF-beta plasma levels after 72 h that might account for enhanced inflammation in PLD2-deficient mice. In contrast to PLD1, TNF-alpha signaling, infarct size and cardiac function 24 h after I/R were not altered when PLD2 was deleted. Furthermore, TGF-beta plasma levels, scar formation and heart function were comparable between PLD2-deficient and control mice 21 days post MI. Conclusions: The present study contributes to our understanding about the role of PLD isoforms and altered platelet signaling in the process of myocardial I/R injury.