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Publication

CLEC4E-Signalling in Myocardial Ischemia-Reperfusion Injury

Book - Dissertation

Inflammation is a key player in the pathogenesis of myocardial infarction. We have previously shown that the pattern recognition receptor CLEC4E is significantly upregulated in peripheral blood of patients with myocardial infarction. However, it remains unknown what the role of CLEC4E is in myocardial ischemia-reperfusion injury. By combining approaches across species we showed that CLEC4E is upregulated in the ischemic myocardium, not only in leukocyte subsets but also in parenchymal cells from the heart. CLEC4E-expression correlates with the extend of acute injury and Clec4e-genetic deletion decreases early leukocyte infiltration into the ischemic myocardium. In vitro analysis revealed an alteration in chemokine-response due to Clec4e-deletion, which could contribute to reduced neutrophil chemotaxis. Long-term follow-up after I/R showed reduced adverse LV-remodeling in Clec4e-knock out, which might be due to the early observed favourable effects on acute injury and inflammation early after I/R. In AMI patiens, CLEC4E in peripheral blood samples correlates with acute injury and LV-function by both microarray as qRT-PCR analysis, confirming our preclinical data. Isolation of leukocyte subsets from these AMI patients show an increase of CLEC4E in the acute phase of MI in neutrophils, monocytes and lymphocytes, with the highest expression in neutrophils. Taken together, our data show that targetting CLEC4E might hold a promising strategy in the treatment of I/R injury in AMI patients.
Publication year:2021
Accessibility:Embargoed