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


ABSTRACT: BACKGROUND:Phospholipase (PL)D1 is crucial for integrin ?IIb?3 activation of platelets in arterial thrombosis and TNF-?-mediated inflammation and TGF-?-mediated collagen scar formation after myocardial infarction (MI) in mice. Enzymatic activity of PLD is not responsible for PLD-mediated TNF-? 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 ?IIb?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-? plasma levels after 72 h that might account for enhanced inflammation in PLD2-deficient mice. In contrast to PLD1, TNF-? signaling, infarct size and cardiac function 24 h after I/R were not altered when PLD2 was deleted. Furthermore, TGF-? 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.

SUBMITTER: Klose AM 

PROVIDER: S-EPMC7247352 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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

Klose Aglaia Maria AM   Klier Meike M   Gorressen Simone S   Elvers Margitta M  

International journal of molecular sciences 20200501 9


<h4>Background</h4>Phospholipase (PL)D1 is crucial for integrin α<sub>IIb</sub>β<sub>3</sub> activation of platelets in arterial thrombosis and TNF-α-mediated inflammation and TGF-β-mediated collagen scar formation after myocardial infarction (MI) in mice. Enzymatic activity of PLD is not responsible for PLD-mediated TNF-α signaling and myocardial healing. The impact of PLD2 in ischemia reperfusion injury is unknown.<h4>Methods</h4>PLD2-deficient mice underwent myocardial ischemia and reperfusio  ...[more]

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