title: Apelin protects myocardial injury induced by isoproterenol in rats.
abstract: We aimed to explore the change in level of apelin and its receptor APJ during myocardial injury and the therapeutic effects of apelin in myocardial injury. Rat myocardial injury was induced by subcutaneous injection of a high dose of isoproterenol (ISO); apelin and APJ mRNA levels were determined by RT-PCR; APJ protein was determined by Western blot; EIA and RIA were used to measure the apelin content and receptor binding, respectively. Plasma lactate dehydrogenase (LDH) activity and myocardial and plasma malondialdehyde (MDA) contents were higher in ISO-treated hearts than that in controls. ISO-treated rats showed lower +/-LV dp/dt(max) values and higher LVEDP value (all P<0.01), which suggested severe heart failure. As well, the apelin content in plasma, atrial and ventricular myocardium was decreased by 27%, 30% and 25% (P<0.01), respectively. The mRNA levels of apelin and APJ in myocardia were also markedly reduced; but the APJ protein level in myocardia was increased. However, administration of apelin significantly ameliorated myocardial injury and ISO-induced heart failure. Compared with the ISO-alone group, the group given low-dosage apelin (5 nmol/kg/day) had 39% and 66% higher +LV dp/dt(max) and -LV dp/dt(max) values, and 40.7% lower LVEDP value (P<0.01), and the leakage of myocardial LDH and increased MDA content were attenuated (all P<0.01). Interestingly, bolus injections of apelin (10 nmol/kg/day) resulted in potent inotropic effects in ISO-treated rats. ISO-induced myocardial injury resulted in hypoexpression of apelin and its receptor APJ, and the administration of exogenous apelin ameliorated heart failure and myocardial injury. Apelin could have a cardioprotective effect, and the apelin-APJ system may be a new therapeutic target in myocardial injury and heart failure.
authors.affiliation: Institute of Cardiovascular Research, Peking University First Hospital, Beijing 100034, China.
authors.forename: Yue-Xia
authors.initials: YX
authors.lastname: Jia
authors.forename: Chun-Shui
authors.initials: CS
authors.lastname: Pan
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Geng
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Helen
authors.initials: H
authors.lastname: Gerns
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Jaw-Kang
authors.initials: JK
authors.lastname: Chang
authors.forename: Chao-Shu
authors.initials: CS
authors.lastname: Tang
authors.forename: Yong-Fen
authors.initials: YF
authors.lastname: Qi
mesh_terms: D000818:Animals; D000073861:Apelin; D000075244:Apelin Receptors; D002352:Carrier Proteins / Q000097:blood / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects; D036341:Intercellular Signaling Peptides and Proteins; D007545:Isoproterenol / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism
chemical_list: D000073861:Apelin; D000075244:Apelin Receptors; C498579:Apln protein, rat; C491284:Aplnr protein, rat; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; D007545:Isoproterenol