Abstract 1222: Endogenous Apelin Maintains Heart Contractility In Aging And Pressure Overload.
Apelin is a newly identified endogenous peptide ligand that binds to APJ, a G-protein coupled receptor which shares significant homology with the angiotensin II type 1 (AT1) receptor. Exogenous Apelin treatments in animals and clinical studies suggested that Apelin-APJ axis constitutes a novel endogenous peptide system involved in a broad range of physiological functions, including cardiovascular function, heart development, control of fluid homeostasis, or obesity. Apelin is also a catalytic substrate for angiotensin converting enzyme 2 (ACE2), the key SARS receptor as well as a critical regulator of cardiovascular functions. The in vivo physiological role of Apelin is still elusive. Here we report the generation of Apelin gene targeted mice. Apelin-mutant mice are viable and fertile, appear healthy, and exhibit normal body weight, water and food intake, heart rates, and heart morphology. Intriguingly, aged Apelin knockout mice developed progressive impairment of cardiac contractility associated with systolic dysfunction in the absence of histological abnormalities. We also report that pressure overload induces upregulation of Apelin expression in the heart. Importantly, in pressure-overload induced heart failure, loss of Apelin did not significantly affect the hypertrophy response, but Apelin mutant mice developed progressive heart failure. Global gene expression arrays and hierarchical clustering of differentially expressed genes in hearts of banded Apelin−/y and Apelin+/y mice showed concerted upregulation of genes involved in extracellular matrix remodelling and muscle contraction. These genetic data show that the endogenous peptide Apelin is crucial to maintain cardiac contractility in pressure overload and aging.