Intermedin is upregulated and has protective roles in a mouse ischemia/reperfusion model.
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.
Zhang
Heng-Yu
HY
Department of Cardiology, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, PR China.
Jiang
Wei
W
Liu
Jian-Ying
JY
Li
Yan
Y
Chen
Chun-Lin
CL
Xin
Hong-Bo
HB
Huang
De-Jia
DJ
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
D009479:Neuropeptides; C514552:intermedin protein, mouse; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase