Hydroxysafflor Yellow A Attenuates Myocardial Ischemia/Reperfusion Injury-induced Platelet Activation: Role of Mitochondrial Function andAutophagy

INTRODUCTION: Platelet activation is a key contributor to myocardial ischemia/ reperfusion (MI/R) injury. Although hydroxysafflor yellow A (HSYA) possesses cardioprotective and antiplatelet properties, its specific mechanisms in modulating platelet activation during MI/R remain unclear. OBJECTIVES: This study investigated how HSYA attenuates MI/R injury by regulating platelet activation. METHODS: An MI/R model was established in mice via ligation of the left anterior descending coronary artery. The regulatory effects of HSYA on platelet activation and mitochondrial function were evaluated via flow cytometry. The mechanisms were analyzed via platelet proteomics. Platelet autophagy was characterized via transmission electron microscopy and western blotting. RESULTS: HSYA significantly attenuated MI/R injury by reducing the myocardial infarct size, improving cardiac function, and decreasing platelet accumulation in the myocardium. HSYA also suppressed platelet activation and enhanced platelet mitochondrial function. Platelet proteomic analysis indicated that the beneficial effects of HSYA were associated primarily with the modulation of proteins involved in energy metabolism and autophagy pathways. Furthermore, HSYA was found to regulate platelet autophagy, as evidenced by both a change in the number of autophagosomes and altered expression of key autophagy-related proteins, including ATG4A, GLIPR2, P62, and LC3. DISCUSSION: Our study provides novel mechanistic insights into how HSYA confers cardioprotection against MI/R injury, highlighting its clinical potential by demonstrating that its effects are mediated at least in part through the modulation of platelet energy metabolism and autophagy. CONCLUSION: HSYA alleviates MI/R injury by inhibiting platelet activation, which is associated with the restoration of mitochondrial function and the modulation of autophagy in platelets.