Key points are not available for this paper at this time.
Abstract Acute myocardial infarction (AMI) is one of the leading causes of death worldwide. Cell apoptosis in the myocardium plays an important role in ischemia and reperfusion (I/R) injury, leading to cardiac damage and dysfunction. Platelets are major players of hemostasis and play a crucial role in vessel occlusion, inflammation and cardiac remodeling after I/R. Here, we studied the impact of platelets on cell apoptosis in the myocardium using a close-chest mouse model of AMI. We found caspase-3 positive resident cardiac cells while leukocytes were negative for caspase-3. Using two different mouse models of thrombocytopenia, we detected a significant reduction of caspase-3 positive cells in the infarct border zone after I/R injury. Further, we identified platelet FasL to induce cell apoptosis via the extrinsic pathway of Fas receptor activation of target cells. Mechanistically, hypoxia triggers platelet adhesion to FasR suggesting that platelet induced apoptosis is elevated after I/R. Platelet-specific FasL knock-out mice showed reduced Bax and BcL-2 expression suggesting that platelets modulate the intrinsic and the extrinsic pathway of apoptosis leading to reduced infarct size after myocardial I/R injury. Therefore, platelet induced cardiac damage needs to be taken into account while optimizing antithrombotic/antiplatelet strategies for patients with AMI.
Krott et al. (Wed,) studied this question.