A novel angiotensin(1-7) agonist, PNA5, reduces ischemic reperfusion injury and cardiac dysfunction.

Introduction: Ischemic heart disease, typically caused by myocardial infarction (MI), is the leading cause of death. Ischemic reperfusion (IR) injury following MI is multifaceted, driven by reactive oxidative species (ROS), calcium overload, and inflammatory responses. Because our novel glycopeptide derivative of Angiotensin-(1-7), PNA5, has an improved half-life, decreases circulating inflammatory cytokines, and inhibits endothelial ROS production, we predict that PNA5 will attenuate IR sequelae post-IR. Methods: Three-month-old C57Bl/6J male mice were subjected to IR and treated subcutaneously, with PNA5 (100 µg/kg/day, Results: Conventional transthoracic echocardiography showed early improvement in ejection fraction by 5 weeks post-IR. Using speckle echocardiography, we demonstrated that PNA5 treatment improved the parameters of strain and dyssynchrony in regional and temporal domains. Global longitudinal strain (GLS) and left ventricular dyssynchrony showed continued dysfunction in untreated animals post-IR, whereas measures of ejection fraction did not. Along with reduced infarct size, PNA5 treatment improved cardiac remodeling, evidenced by reduced scarring within the midapical regions of the heart compared with untreated animals. Conclusion: These data suggest that PNA5 treatments improve heart outcomes post-IR and could potentially be a therapeutic for IR injury; measures of GLS and dyssynchrony may provide more relevant insight into the protective effects of PNA5.