Post-infarct treatment with [Pyr(1)]apelin-13 improves myocardial function by increasing neovascularization and overexpression of angiogenic growth factors in rats.
Ischemic heart disease is the leading cause of mortality in the world. Angiogenesis is important for cardiac repair after myocardial infarction (MI) as restores blood supply to the ischemic myocardium and preserves cardiac function. Apelin is a peptide that has been recently shown to potentiate angiogenesis. The aim of this study was to investigate angiogenic effects of [Pyr(1)]apelin-13 in the rat model of post-MI. Male Wistar rats (n=36) were randomly divided into three groups: (1) sham (2) MI and (3) MI treated with [Pyr(1)]apelin-13 (MI+Apel). MI animals were subjected to 30min left anterior descending coronary artery (LAD) ligation and 14 days of reperfusion. Twenty-four hours after LAD ligation, [Pyr(1)]apelin-13 (10nmol/kg/day) was administered i.p. for 5 days. Hemodynamic functions by catheter introduced into the left ventricle (LV), myocardial fibrosis by Masson׳s trichrome staining, gene expression of vascular endothelial growth factor-A (VEGFA), VEGF receptor-2 (Kdr), Ang-1 (angiopoietin-1), Tie2 (tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 2) and eNOS by Real-time polymerase chain reaction (Real-Time PCR) and myocardial angiogenesis by CD31 imunostaining were assessed at day 14 post-MI. Post-infarct treatment with [Pyr(1)]apelin-13 improved LV function and decreased myocardial fibrosis. [Pyr(1)]apelin-13 treatment led to a significant increase in the expression of VEGFA, Kdr, Ang-1, Tie2 and eNOS. Further, treatment with [Pyr(1)]apelin-13 promoted capillary density. [Pyr(1)]apelin-13 has angiogenic and anti-fibrotic activity via formation of new blood vessels and overexpression of VEGFA, Kdr, Ang-1, Tie2 and eNOS in the infarcted myocardium which could in turn repair myocardium and improve LV function.
Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran.
Yaser
Y
Azizi
Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran. Electronic address: faghihim@sina.tums.ac.ir.
Mahdieh
M
Faghihi
Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran.
Alireza
A
Imani
Neurophysiology Research Center, Shahed University, Tehran, Islamic Republic of Iran.
Mehrdad
M
Roghani
Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran.
Ali
A
Zekri
Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran.
Maryam Beigom
MB
Mobasheri
Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran.
Tayebeh
T
Rastgar
Department of Physiology, School of Medicine, Gonabad University of Medical Sciences, Gonabad, Islamic Republic of Iran.
Maryam
M
Moghimian
D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism*; D042683:Angiopoietin-1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D005355:Fibrosis; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D042787:Receptor, TIE-2 / Q000235:genetics / Q000378:metabolism; D020127:Recovery of Function; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects*
D042501:Angiogenic Proteins; D042683:Angiopoietin-1; C467629:Angpt1 protein, rat; D002316:Cardiotonic Agents; D036341:Intercellular Signaling Peptides and Proteins; D042461:Vascular Endothelial Growth Factor A; C586143:apelin 13, Pyr(1)-; C467498:vascular endothelial growth factor A, rat; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C000602029:Kdr protein, rat; D042787:Receptor, TIE-2; D040301:Vascular Endothelial Growth Factor Receptor-2
Ang-1; Myocardial angiogenesis; Rat; VEGFA; [Pyr(1)]apelin-13; eNOS