Abstract 17991: The Cardiolipin-targeting Peptide Bendavia Protects Post-ischemic Myocardium by Preserving Mitochondrial Membrane Fluidity

Bendavia is a mitochondria-targeting peptide currently being tested in the EMBRACE-STEMI trial for reducing injury during acute coronary syndromes. Across pre-clinical models, Bendavia preserves mitochondrial function by targeting the mitochondrial phospholipid cardiolipin, but it is not understood how targeting cardiolipin ultimately leads to cardioprotection. Membrane fluidity, which regulates the assembly of mitochondrial proteins, is directly influenced by cardiolipin levels/content. We recently observed augmented fluidity with Bendavia in cardiolipin-enriched lipid vesicles, but the pathophysiological relevance has not been established. We hypothesized that mitochondrial membrane fluidity would be decreased after cardiac reperfusion, and that targeting cardiolipin with Bendavia protects tissue by sustaining mitochondrial membrane fluidity. Following ex vivo ischemia-reperfusion, rat left ventricular mitochondria were isolated and mitochondrial membrane fluidity was assessed. We utilized two different...