FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2803611493> ?p ?o ?g. }

• W2803611493 endingPage "H356" @default.
• W2803611493 startingPage "H348" @default.
• W2803611493 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 treated with apelin exhibited decreased phosphorylation in cardiac troponin I NH2-terminal residues (Ser22 and Ser23) consistent with increased Ca2+ sensitivity. These data establish that APJ stretch transduction is mediated specifically by myocardial APJ, that APJ is necessary for stretch-induced increases in contractility, and that apelin opposes APJ's stretch-mediated hypertrophy signaling by lowering Ca2+ transients while maintaining contractility through myofilament Ca2+ sensitization. These findings underscore apelin's unique potential as a therapeutic agent that can simultaneously support cardiac function and protect against the hypertrophy-heart failure transition. NEW & NOTEWORTHY These data address fundamental gaps in our understanding of apelin-APJ signaling in heart failure by localizing APJ's ligand-independent stretch sensing to the myocardium, identifying a novel mechanism of apelin-APJ inotropy via myofilament Ca2+ sensitization, and identifying potential mitigating effects of apelin in APJ stretch-induced hypertrophic signaling." @default.
• W2803611493 created "2018-06-01" @default.
• W2803611493 creator A5003486121 @default.
• W2803611493 creator A5016780098 @default.
• W2803611493 creator A5018329599 @default.
• W2803611493 creator A5035282947 @default.
• W2803611493 creator A5049149323 @default.
• W2803611493 creator A5051232840 @default.
• W2803611493 creator A5053248273 @default.
• W2803611493 creator A5057606234 @default.
• W2803611493 creator A5058198453 @default.
• W2803611493 creator A5061808340 @default.
• W2803611493 creator A5070273499 @default.
• W2803611493 creator A5072203009 @default.
• W2803611493 creator A5073639811 @default.
• W2803611493 creator A5075711252 @default.
• W2803611493 creator A5086972884 @default.
• W2803611493 date "2018-08-01" @default.
• W2803611493 modified "2023-10-14" @default.
• W2803611493 title "Apelin and APJ orchestrate complex tissue-specific control of cardiomyocyte hypertrophy and contractility in the hypertrophy-heart failure transition" @default.
• W2803611493 cites W1985043641 @default.
• W2803611493 cites W1987893946 @default.
• W2803611493 cites W1989706089 @default.
• W2803611493 cites W1992782760 @default.
• W2803611493 cites W1993913999 @default.
• W2803611493 cites W2009881954 @default.
• W2803611493 cites W2009953198 @default.
• W2803611493 cites W2013824152 @default.
• W2803611493 cites W2014447414 @default.
• W2803611493 cites W2017965023 @default.
• W2803611493 cites W2019301043 @default.
• W2803611493 cites W2022701671 @default.
• W2803611493 cites W2027000467 @default.
• W2803611493 cites W2027772810 @default.
• W2803611493 cites W2033585364 @default.
• W2803611493 cites W2036739087 @default.
• W2803611493 cites W2043505422 @default.
• W2803611493 cites W2060660919 @default.
• W2803611493 cites W2061800712 @default.
• W2803611493 cites W2071935182 @default.
• W2803611493 cites W2073164220 @default.
• W2803611493 cites W2075714512 @default.
• W2803611493 cites W2076953147 @default.
• W2803611493 cites W2076996105 @default.
• W2803611493 cites W2089330954 @default.
• W2803611493 cites W2089394474 @default.
• W2803611493 cites W2093213355 @default.
• W2803611493 cites W2095966074 @default.
• W2803611493 cites W2101929550 @default.
• W2803611493 cites W2107390778 @default.
• W2803611493 cites W2111133464 @default.
• W2803611493 cites W2113953774 @default.
• W2803611493 cites W2117196163 @default.
• W2803611493 cites W2120593855 @default.
• W2803611493 cites W2123655257 @default.
• W2803611493 cites W2127087522 @default.
• W2803611493 cites W2130674647 @default.
• W2803611493 cites W2132493114 @default.
• W2803611493 cites W2134208169 @default.
• W2803611493 cites W2136125096 @default.
• W2803611493 cites W2137654131 @default.
• W2803611493 cites W2138295923 @default.
• W2803611493 cites W2139032664 @default.
• W2803611493 cites W2139339310 @default.
• W2803611493 cites W2140313980 @default.
• W2803611493 cites W2152509794 @default.
• W2803611493 cites W2157061673 @default.
• W2803611493 cites W2164364796 @default.
• W2803611493 cites W2165312739 @default.
• W2803611493 cites W2340059643 @default.
• W2803611493 cites W2619631352 @default.
• W2803611493 cites W2621842508 @default.
• W2803611493 cites W2753088052 @default.
• W2803611493 cites W2756104676 @default.
• W2803611493 cites W61964868 @default.
• W2803611493 cites W992469840 @default.
• W2803611493 doi "https://doi.org/10.1152/ajpheart.00693.2017" @default.
• W2803611493 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6139625" @default.
• W2803611493 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29775410" @default.
• W2803611493 hasPublicationYear "2018" @default.
• W2803611493 type Work @default.
• W2803611493 sameAs 2803611493 @default.
• W2803611493 citedByCount "26" @default.
• W2803611493 countsByYear W28036114932019 @default.
• W2803611493 countsByYear W28036114932020 @default.
• W2803611493 countsByYear W28036114932021 @default.
• W2803611493 countsByYear W28036114932022 @default.
• W2803611493 countsByYear W28036114932023 @default.
• W2803611493 crossrefType "journal-article" @default.
• W2803611493 hasAuthorship W2803611493A5003486121 @default.
• W2803611493 hasAuthorship W2803611493A5016780098 @default.
• W2803611493 hasAuthorship W2803611493A5018329599 @default.
• W2803611493 hasAuthorship W2803611493A5035282947 @default.
• W2803611493 hasAuthorship W2803611493A5049149323 @default.
• W2803611493 hasAuthorship W2803611493A5051232840 @default.
• W2803611493 hasAuthorship W2803611493A5053248273 @default.
• W2803611493 hasAuthorship W2803611493A5057606234 @default.
• W2803611493 hasAuthorship W2803611493A5058198453 @default.

• next