Stanford Medicine


Role of Apelin - APJ in Cardiovascular Disease

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Heart failure is a leading cause of hospitalization and the most costly cardiovascular disorder in the United States. Despite its enormous human and economic burden, there is little consensus as to the optimum treatment for decompensated function. Further, longstanding concerns over the increased mortality associated with inotropic agents,  combined with newer concerns over the consequences of traditional diuretics and more recently approved agents such as nesiritide leave few options for the evidence-based care of this group of patients. New approaches which target upstream of traditional agents are urgently required.

In 2003, we demonstrated the importance of a novel neurohumoral pathway in human heart failure. Specifically, transcription profiling of human left ventricles (LV) revealed that expression of the G protein coupled APJ receptor was more significantly upregulated than any other gene following offloading with a left ventricular assist device. We went on since then to localize the receptor and its recently discovered ligand, apelin, through the development of antibodies to both, work with a local company to refine an immunoassay kit for the measurement of protein levels, characterize both acute and hemodynamic consequences to apelin infusion, and assay plasma levels of apelin in cohorts of heart failure patients. We are fortunate to work closely with Dr Thomas Quertermous and share transgenic mouse models which include apelin null, APJ null and most recently, conditional, tissue specific knockout models of APJ. With a therapeutic potential that includes vasopressin antagonism, nitric oxide mediated vasodilation, renin-angiotensin system (RAS) counter-regulation, and enhanced contractile reserve through calcium sensitization, translation of this promising agent to the clinic is timely.