Apelin protects heart against ischemia/reperfusion injury in rat.
Apelin, the endogenous ligand of the G protein-coupled APJ receptor, is a peptide mediator with emerging regulatory actions in the heart. We aimed to determine whether the endogenous apelin/APJ system is an intrinsic protective pathway in ischemic/reperfusion injury. A Langendorff model of perfused isolated rat hearts and primary cultured myocardial cells from neonatal rats were used. Cardiac function was monitored and apelin/APJ expression was determined by real-time PCR and Western blot analysis. In rats under I/R, cardiac function was significantly decreased as compared with controls, and APJ was over-expressed at both the mRNA and protein levels (by 7-fold and 35%, respectively, both p<0.01). However, pre-administration of apelin (30pmol/L) greatly ameliorated the reduced heart function. To gain mechanistic insight into the cardio-protective effects of apelin/APJ, cultured cardiomyocytes were treated with apelin (30 pmol/L), and those under hypoxia/re-oxygenation showed H/R-induced apoptosis and up-regulated apelin/APJ mRNA expression by 6-fold and 7-fold, respectively (both p<0.01). And lactate dehydrogenase leakage was greatly increased as well. Meanwhile, apoptosis, the generation of reactive oxygen species and malonaldehyde content as well as lactate dehydrogenase leakage were inhibited by apelin. Furthermore, apelin enhanced superoxide dismutase activity and phosphorylation of extracellular signal-regulated kinase 1/2 and Akt after hypoxia/re-oxygenation. In conclusion, apelin/APJ has protective effects in ischemic heart disease and might constitute an important therapy target.
Zeng
Xiang Jun
XJ
Department of Pathophysiology, Capital Medical University, Beijing, China.
Zhang
Li Ke
LK
Wang
Hong Xia
HX
Lu
Ling Qiao
LQ
Ma
Li Quan
LQ
Tang
Chao Shu
CS
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D000075244:Apelin Receptors; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D005419:Flavonoids / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D000077191:Wortmannin
D000730:Androstadienes; D000075244:Apelin Receptors; C491284:Aplnr protein, rat; D005419:Flavonoids; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; C495199:apelin-13 peptide; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000077191:Wortmannin