Platelets induce endothelial cell mitochondrial dysfunction in myocardial infarction.

Summary

Platelet releasates from MI patients disrupted endothelial mitochondrial potential and networks. Multi-omics identified CCL3 upregulation in MI platelets as a key mediator; CCR5 blockade attenuated these effects. In a cohort of 261 patients with established CVD, higher circulating CCL3 associated with incident MACE, linking platelet activation to endothelial dysfunction and outcomes.

Key Findings

• MI platelet releasates decreased endothelial mitochondrial membrane potential and disrupted mitochondrial networks.
• CCL3 was upregulated in MI platelets and mediated endothelial mitochondrial dysfunction; CCR5 blockade attenuated effects.
• Higher circulating CCL3 levels predicted incident major adverse cardiovascular events in an independent cohort (n=261).

Clinical Implications

Suggests CCL3/CCR5 as a therapeutic target to mitigate coronary endothelial damage in MI and highlights circulating CCL3 as a potential risk stratification biomarker.

Limitations

• Causality for clinical outcomes not established without intervention trials
• Size of clinical association cohort (n=261) limits subgroup analyses and external generalizability

Future Directions

Test CCR5 antagonism or CCL3 neutralization to prevent microvascular injury in MI, and evaluate CCL3-guided risk stratification in larger prospective cohorts.