title: Intermedin is upregulated and has protective roles in a mouse ischemia/reperfusion model.
abstract: Intermedin (IMD), a new calcitonin/calcitonin gene-related peptide family peptide with vasodilatory and positive inotropic properties, has multiple functions in regulating cardiovascular homeostasis and is of particular interest in the pathophysiology of myocardial ischemia/reperfusion (MI/R). We created a mouse model of MI/R by ligating the cardiac left anterior descending artery to study the possible pathophysiological role of IMD and its receptor complexes in MI/R. Compared with the control, infarcted mice showed increased content, mRNA and protein expression of IMD in plasma and cardiac tissue. The mRNA expression of the receptor activity-modifying protein 3 (RAMP3) gene increased very early, and the calcitonin receptor-like receptor and RAMP2 mRNA levels increased later after reperfusion. However, the RAMP1 gene expression did not change. The tissue IMD content was positively correlated with the diastolic blood pressure and negatively correlated with pulse pressure. In addition, exogenous IMD treatment significantly ameliorated the MI/R injury by rescuing the pulse pressure, inhibiting neutrophil infiltration in the peri-infarction area, and decreasing the creatine kinase and lactate dehydrogenase activities in plasma. Our results indicated that IMD was upregulated in the ischemic myocardium and may induce important beneficial cytoprotection against cardiac ischemic injury.
authors.affiliation: Department of Cardiology, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, PR China.
authors.forename: Heng-Yu
authors.initials: HY
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Jian-Ying
authors.initials: JY
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Chun-Lin
authors.initials: CL
authors.lastname: Chen
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Xin
authors.forename: De-Jia
authors.initials: DJ
authors.lastname: Huang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003402:Creatine Kinase / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D007150:Immunohistochemistry; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009203:Myocardial Infarction / Q000235:genetics / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000473:pathology*; D009479:Neuropeptides / Q000096:biosynthesis* / Q000138:chemical synthesis / Q000235:genetics; D020556:Neutrophil Infiltration / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D009479:Neuropeptides; C514552:intermedin protein, mouse; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase