Apelin-13 attenuates experimental sepsis-associated myocardial injury in association with reduced endoplasmic reticulum stress and mitochondrial dysfunction

Sepsis-associated myocardial injury is driven by interacting inflammatory, oxidative, endoplasmic reticulum (ER), and mitochondrial stress responses. This study investigated whether Apelin-13 protects against myocardial injury during experimental sepsis. Male Sprague-Dawley rats were assigned to sham-operated control, cecal ligation and puncture (CLP), or CLP plus Apelin-13 groups. Apelin-13 was administered intraperitoneally after CLP, and blood and myocardial tissues were collected at 48 h. In parallel, H9c2 cardiomyoblasts were pretreated with Apelin-13 before lipopolysaccharide challenge. CLP caused myocardial histopathological injury, inflammatory cell infiltration, increased circulating interleukin-1β and tumor necrosis factor-α, and increased myocardial GRP78, MLKL, and cleaved caspase-3 immunoreactivity. These changes were attenuated by Apelin-13. In H9c2 cells, Apelin-13 improved viability, reduced lactate dehydrogenase release, decreased GRP78, PERK, CHOP, Bax, and cleaved caspase-3 abundance, and restored Bcl-xL expression. Apelin-13 also reduced intracellular and mitochondrial reactive oxygen species and partially preserved mitochondrial membrane potential. Thus, Apelin-13 attenuated experimental sepsis-associated myocardial and cardiomyoblast injury, an effect associated with reduced inflammation and ER stress and improved mitochondrial homeostasis.