title: Downregulation of endogenous intermedin augmented myocardial injury in rats with ischemia/reperfusion.
abstract: Intermedin (IMD) plays an important regulatory role in cardiovascular function. We aimed to explore the protein expression of IMD and its receptors, calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins (RAMPs), and the role of endogenous IMD in myocardial ischemia/reperfusion (I/R) injury in rats. The rat model of I/R was created by ligating cardiac left anterior descending artery. Western blot was used to determine protein expression of CRLR and RAMPs, and radioimmunoassay was used to detect IMD content. Compared with control, protein levels of CRLR and RAMPs in both ischemic and nonischemic region were upregulated at different stages of reperfusion. IMD protein content in nonischemic area myocardium also increased. However, IMD protein content in ischemic area downregulated at 3-, 6-, and 12-h reperfusion. In hypoxia/reoxygenation model of neonatal cardiomyocytes, IMD attenuated myocyte injury, and IMD receptor antagonist IMD17-47 aggravated myocyte impairment by blocking endogenous IMD. In conclusion, the downregulation of IMD at early stage of reperfusion might augment myocardium injury.
authors.affiliation: The Key Laboratory of Remodeling-related Cardiovascular Diseases, Capital Medical University, Ministry of Education, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Teng
authors.forename: Y
authors.initials: Y
authors.lastname: Bian
authors.forename: Y
authors.initials: Y
authors.lastname: Cai
authors.forename: X
authors.initials: X
authors.lastname: Duan
authors.forename: F
authors.initials: F
authors.lastname: Yuan
authors.forename: J
authors.initials: J
authors.lastname: Du
authors.forename: W
authors.initials: W
authors.lastname: Wu
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: C
authors.initials: C
authors.lastname: Tang
authors.forename: Y
authors.initials: Y
authors.lastname: Qi
mesh_terms: D053607:Adrenomedullin / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D058286:Calcitonin Receptor-Like Protein / Q000378:metabolism; D015536:Down-Regulation; D004562:Electrocardiography; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D009479:Neuropeptides / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D058261:Receptor Activity-Modifying Proteins / Q000378:metabolism; D014463:Ultrasonography
chemical_list: C499411:Adm2 protein, rat; D058286:Calcitonin Receptor-Like Protein; D009479:Neuropeptides; D058261:Receptor Activity-Modifying Proteins; D053607:Adrenomedullin