Biomedicines (May 2024)

Platelets Induce Cell Apoptosis of Cardiac Cells via FasL after Acute Myocardial Infarction

  • Kim J. Krott,
  • Friedrich Reusswig,
  • Matthias Dille,
  • Evelyn Krüger,
  • Simone Gorressen,
  • Saoussen Karray,
  • Amin Polzin,
  • Malte Kelm,
  • Jens W. Fischer,
  • Margitta Elvers

DOI
https://doi.org/10.3390/biomedicines12051077
Journal volume & issue
Vol. 12, no. 5
p. 1077

Abstract

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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 in 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 in 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 Bcl2 expression, suggesting that platelets modulate the intrinsic and extrinsic pathways of apoptosis, leading to reduced infarct size after myocardial I/R injury. Thus, a new mechanism for how platelets contribute to tissue homeostasis after AMI was identified that should be validated in patients soon.

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