AIMS: Apelin, an endogenous cytokine, has a number of biological effects on the cardiovascular system, including a cardioprotective effect and calcium modulation. Because the intracellular calcium abnormality is considered to play an important role in cardiac dysfunction induced by ischaemia-reperfusion (I/R), the aim of this study was to examine the effects of apelin-13 on I/R-induced changes in cardiac performance and sarcoplasmic reticulum (SR) function. METHODS AND RESULTS: Isolated rat hearts were subjected to global ischaemia followed by reperfusion in the absence or presence of apelin-13 and inhibitors of some survival kinases. We found that depressed cardiac performance induced by I/R was attenuated by apelin-13. Furthermore, apelin-13 depressed oxidative stress during I/R. SR function depressed during I/R was partly reversed by apelin-13. SR oxidative modification levels were increased in I/R and reversed by apelin. Inhibitors of phosphatidylinositol-3-kinase and protein kinase C abolished the effects of apelin. Apelin-13 maintained the Ca(2+) transient against I/R in cardiomyocytes. CONCLUSION: Apelin protects SR function and cardiac performance during I/R by attenuating oxidation of sarco(endo)plasmic reticulum Ca(2+)-ATPase and RyR.
AIMS: Apelin, an endogenous cytokine, has a number of biological effects on the cardiovascular system, including a cardioprotective effect and calcium modulation. Because the intracellular calcium abnormality is considered to play an important role in cardiac dysfunction induced by ischaemia-reperfusion (I/R), the aim of this study was to examine the effects of apelin-13 on I/R-induced changes in cardiac performance and sarcoplasmic reticulum (SR) function. METHODS AND RESULTS: Isolated rat hearts were subjected to global ischaemia followed by reperfusion in the absence or presence of apelin-13 and inhibitors of some survival kinases. We found that depressed cardiac performance induced by I/R was attenuated by apelin-13. Furthermore, apelin-13 depressed oxidative stress during I/R. SR function depressed during I/R was partly reversed by apelin-13. SR oxidative modification levels were increased in I/R and reversed by apelin. Inhibitors of phosphatidylinositol-3-kinase and protein kinase C abolished the effects of apelin. Apelin-13 maintained the Ca(2+) transient against I/R in cardiomyocytes. CONCLUSION:Apelin protects SR function and cardiac performance during I/R by attenuating oxidation of sarco(endo)plasmic reticulum Ca(2+)-ATPase and RyR.
Authors: Julia J Mack; Thiago S Mosqueiro; Brian J Archer; William M Jones; Hannah Sunshine; Guido C Faas; Anais Briot; Raquel L Aragón; Trent Su; Milagros C Romay; Austin I McDonald; Cheng-Hsiang Kuo; Carlos O Lizama; Timothy F Lane; Ann C Zovein; Yun Fang; Elizabeth J Tarling; Thomas Q de Aguiar Vallim; Mohamad Navab; Alan M Fogelman; Louis S Bouchard; M Luisa Iruela-Arispe Journal: Nat Commun Date: 2017-11-20 Impact factor: 14.919