Higher circulating CCL3 levels, a key mediator of platelet-induced endothelial mitochondrial dysfunction, were associated with incident major adverse cardiovascular events in patients with established CVD.
Cohort (n=261)
Do platelet-released factors, specifically CCL3, induce endothelial cell mitochondrial dysfunction in myocardial infarction?
Platelet-derived CCL3 mediates endothelial mitochondrial dysfunction during myocardial infarction and correlates with adverse clinical outcomes, identifying a potential mechanistic link and therapeutic target.
Coronary endothelial dysfunction plays a key role in the pathogenesis of acute coronary syndromes. During myocardial infarction (MI), activated platelets release prothrombotic and proinflammatory factors, contributing to vascular injury and dysfunction. To investigate platelet-mediated endothelial dysfunction, endothelial cells (ECs) were treated with platelet-released factors from patients with MI and non-MI controls undergoing coronary angiography. RNA sequencing revealed that MI platelets induced EC mitochondrial dysfunction, confirmed by reduced mitochondrial membrane potential and disrupted mitochondrial networks. Integrating platelet transcriptomic data, we identified the C-C motif chemokine ligand 3 (CCL3) as significantly up-regulated in MI platelets and a key mediator of EC mitochondrial dysfunction. Blocking its receptor, CCR5, attenuated CCL3 effects. In an independent cohort of 261 patients with established cardiovascular disease, higher circulating CCL3 levels were associated with incident major adverse cardiovascular events. Together, these findings establish a mechanistic link between platelet activation and coronary endothelial dysfunction in MI.
Sun et al. (Fri,) conducted a cohort in Myocardial infarction and established cardiovascular disease (n=261). Higher circulating CCL3 levels was evaluated on Incident major adverse cardiovascular events. Higher circulating CCL3 levels, a key mediator of platelet-induced endothelial mitochondrial dysfunction, were associated with incident major adverse cardiovascular events in patients with established CVD.