Extracellular Vesicles Modulation by an Adiponectin Receptor Agonist Provides Cardioprotection for Myocardial Ischemic Injury

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Ischemic heart disease is a leading cause of global morbidity and mortality, with more effective clinical therapies needed to mitigate cardiac ischemic injury. Extracellular vesicles (EVs) mediate intercellular communication in cardiac pathophysiology. Adiponectin mediates cardioprotective effects yet its relationship with EVs biology remains unexplored. We investigated whether ALY688, an adiponectin receptor agonist, modulates EV biogenesis and cargo to confer cardioprotection in a mouse model of myocardial infarction (MI). ALY688 (15 mg/kg daily for 28 days) significantly attenuated MI-induced cardiac dysfunction, reduced infarct size, and decreased fibrotic scar in both lean mice on standard chow and obese mice fed a high-fat diet. Plasma EVs were isolated and while MI reduced circulating EV numbers, ALY688 restored EV production and enhanced loading with bioactive adiponectin. In addition, proteomic analysis revealed ALY688-shaped EVs were enriched in metabolism regulated proteins. The direct functional effects and mechanisms of EV action were examined in iPSC-derived cardiomyocytes and H9c2 cells. EV from ALY688 treated mice (EV ALY ) reduced hypoxia-induced apoptosis, cell death, and ROS accumulation while restoring mitochondrial function and enhancing autophagy flux, whereas EV from control mice did not. Importantly, intervention with systemic EV ALY administration to mi

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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