Sympathetic hyperexcitation occurs after myocardial infarction (MI), increasing oxygen demand, promoting adverse cardiac remodeling, and contributing to heart failure progression and poor prognosis. Apelin, acting through its receptor APJ, is expressed in cardiovascular regulatory brain regions and has been implicated in blood pressure and sympathetic regulation. We hypothesized that altered central apelin–APJ signaling contributes to neurohumoral activation and cardiac remodeling following MI. To test this, we examined APJ expression in the paraventricular nucleus (PVN), nucleus tractus solitarius (NTS), and rostral ventrolateral medulla (RVLM) of rats after MI induced by coronary artery ligation using qPCR and Western blot analysis. APJ expression was significantly increased in the PVN. Immunohistochemistry further revealed that APJ was localized on neuronal membranes within the PVN. To determine functional consequences, APJ expression in the PVN was selectively silenced using viral vector–mediated overexpression of APJ shRNA. Neurohumoral activation, sympathetic activity, cardiac function, and structural remodeling were subsequently assessed in rats receiving APJ shRNA or a scrambled control. Selective APJ silencing in the PVN markedly reduced sympathetic nerve activity, plasma norepinephrine, and arginine vasopressin levels. Moreover, APJ knockdown attenuated adverse cardiac remodeling and improved cardiac function in MI rats. These findings indicate that the central apelin–APJ system in the PVN is a critical mediator of sympathoexcitation and cardiac pathophysiology after MI. In conclusion, our study identifies hypothalamic apelin–APJ signaling as a key regulator of sympathetic outflow and cardiac remodeling in MI-associated heart failure. Targeting central APJ signaling may represent a novel therapeutic strategy for mitigating neurohumoral activation and disease progression in MI-associated heart failure. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Mareddy et al. (Fri,) studied this question.