APLNR and heart failure: Our previous study recombined the short peptide ELA-21 and the Fc fragment of human IgG into a long-acting Fc-ELA-21 fusion protein and has shown that Fc-ELA-21′half-life in mice is 44 h and retained activation of the APJ receptor to exert anti-heart failure activity However, the anti-heart failure mechanisms of Fc-ELA-21 are still unclear, and its optimal dose range and long-term in vivo safety profile remain undefinedThis study aimed to investigate the anti-heart failure mechanisms of Fc-ELA-21, dose range, and in vivo safety.