Apelin and APJ orchestrate complex tissue-specific control of cardiomyocyte hypertrophy and contractility in the hypertrophy-heart failure transition

American Journal of Physiology. Heart and Circulatory Physiology
Victoria N ParikhEuan A Ashley

Abstract

The G protein-coupled receptor APJ is a promising therapeutic target for heart failure. Constitutive deletion of APJ in the mouse is protective against the hypertrophy-heart failure transition via elimination of ligand-independent, β-arrestin-dependent stretch transduction. However, the cellular origin of this stretch transduction and the details of its interaction with apelin signaling remain unknown. We generated mice with conditional elimination of APJ in the endothelium (APJendo-/-) and myocardium (APJmyo-/-). No baseline difference was observed in left ventricular function in APJendo-/-, APJmyo-/-, or control (APJendo+/+, APJmyo+/+) mice. After exposure to transaortic constriction, APJendo-/- mice displayed decreased left ventricular systolic function and increased wall thickness, whereas APJmyo-/- mice were protected. At the cellular level, carbon fiber stretch of freshly isolated single cardiomyocytes demonstrated decreased contractile responses to stretch in APJ-/- cardiomyocytes compared with APJ+/+ cardiomyocytes. Ca2+ transients did not change with stretch in either APJ-/- or APJ+/+ cardiomyocytes. Application of apelin to APJ+/+ cardiomyocytes resulted in decreased Ca2+ transients. Furthermore, hearts of mice treate...Continue Reading

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Citations

Jan 13, 2019·International Journal of Molecular Sciences·Teruki SatoKeiji Kuba
Mar 1, 2019·The Journal of Physiology·Andrea CollivaSerena Zacchigna
Sep 5, 2020·Journal of Cellular Physiology·Wentao ChenTizhong Shan
Jun 27, 2019·Annals of the New York Academy of Sciences·Eric MarsaultMannix Auger-Messier
May 21, 2020·Diabetes Therapy : Research, Treatment and Education of Diabetes and Related Disorders·Alexander E Berezin, Alexander A Berezin
Feb 27, 2021·American Journal of Physiology. Heart and Circulatory Physiology·David CoquerelOlivier Lesur
Apr 11, 2021·Molecular and Cellular Endocrinology·I Castan-LaurellP Valet
Apr 30, 2021·Scientific Reports·Ana Elisa T S de CarvalhoRegina C Spadari
Mar 22, 2021·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Peter JanssensDjalila Mekahli

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Methods Mentioned

BETA
genotyping

Software Mentioned

MATLAB
IonOptix
ImageJ

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