Elevated platelet–leukocyte complexes are associated with, but dispensable for myocardial ischemia–reperfusion injury

Aims P-selectin is an activatable adhesion molecule on platelets promoting platelet aggregation, and platelet–leukocyte complex (PLC) formation. Increased numbers of PLC are circulating in the blood of patients shortly after acute myocardial infarction and predict adverse outcomes. These correlation...

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Bibliographic Details
Published in:Basic research in cardiology 2022-12, Vol.117 (1), p.61-61, Article 61
Main Authors: Starz, Christopher, Härdtner, Carmen, Mauler, Maximilian, Dufner, Bianca, Hoppe, Natalie, Krebs, Katja, Ehlert, Carolin Anna, Merz, Julian, Heidt, Timo, Stachon, Peter, Wolf, Dennis, Bode, Christoph, von zur Muehlen, Constantin, Rottbauer, Wolfgang, Gawaz, Meinrad, Duerschmied, Daniel, Leuschner, Florian, Borst, Oliver, Westermann, Dirk, Hilgendorf, Ingo
Format: Article
Language:English
Subjects:
Adhesion
Animals
Blood circulation
Blood platelets
Blood vessels
Bone marrow
Cardiology
Echocardiography
Flow cytometry
Gene expression
Heart attacks
Injuries
Ischemia
Leukocytes
Medicine
Medicine & Public Health
Mice
Myocardial infarction
Myocardial Infarction - metabolism
Myocardial ischemia
Myocardial Ischemia - metabolism
Myocardial Reperfusion Injury - metabolism
Original Contribution
P-selectin
P-Selectin - metabolism
Platelet aggregation
Platelets
Reperfusion
Reperfusion Injury - metabolism
Therapeutic targets
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Summary:Aims P-selectin is an activatable adhesion molecule on platelets promoting platelet aggregation, and platelet–leukocyte complex (PLC) formation. Increased numbers of PLC are circulating in the blood of patients shortly after acute myocardial infarction and predict adverse outcomes. These correlations led to speculations about whether PLC may represent novel therapeutic targets. We therefore set out to elucidate the pathomechanistic relevance of PLC in myocardial ischemia and reperfusion injury. Methods and results By generating P-selectin deficient bone marrow chimeric mice, the post-myocardial infarction surge in PLC numbers in blood was prevented. Yet, intravital microscopy, flow cytometry and immunohistochemical staining, echocardiography, and gene expression profiling showed unequivocally that leukocyte adhesion to the vessel wall, leukocyte infiltration, and myocardial damage post-infarction were not altered in response to the lack in PLC. Conclusion We conclude that myocardial infarction associated sterile inflammation triggers PLC formation, reminiscent of conserved immunothrombotic responses, but without PLC influencing myocardial ischemia and reperfusion injury in return. Our experimental data do not support a therapeutic concept of selectively targeting PLC formation in myocardial infarction.
ISSN:0300-8428
1435-1803
DOI:10.1007/s00395-022-00970-3