title: Apelin-13 increases myocardial progenitor cells and improves repair postmyocardial infarction.
abstract: Apelin is an endogenous ligand for the angiotensin-like 1 receptor (APJ) and has beneficial effects against myocardial ischemia-reperfusion injury. Little is known about the role of apelin in the homing of vascular progenitor cells (PCs) and cardiac functional recovery postmyocardial infarction (post-MI). The present study investigated whether apelin affects PC homing to the infarcted myocardium, thereby mediating repair and functional recovery post-MI. Mice were infarcted by coronary artery ligation, and apelin-13 (1 mg·kg(-1)·day(-1)) was injected for 3 days before MI and for 14 days post-MI. Homing of vascular PCs [CD133(+)/c-Kit(+)/Sca1(+), CD133(+)/stromal cell-derived factor (SDF)-1α(+), and CD133(+)/CXC chemokine receptor (CXCR)-4(+)] into the ischemic area was examined. Myocardial Akt, endothelial nitric oxide synthase (eNOS), VEGF, jagged1, notch3, SDF-1α, and CXCR-4 expression were assessed at 24 h and 14 days post-MI. Functional analyses were performed on day 14 post-MI. Mice that received apelin-13 treatment demonstrated upregulation of SDF-1α/CXCR-4 expression and dramatically increased the number of CD133(+)/c-Kit(+)/Sca1(+), CD133(+)/SDF-1α(+), and c-Kit(+)/CXCR-4(+) cells in infarcted hearts. Apelin-13 also significantly increased Akt and eNOS phosphorylation and upregulated VEGF, jagged1, and notch3 expression in ischemic hearts. This was accompanied by a significant reduction of myocardial apoptosis. Furthermore, treatment with apelin-13 promoted myocardial angiogenesis and attenuated cardiac fibrosis and hypertrophy together with a significant improvement of cardiac function at 14 days post-MI. Apelin-13 increases angiogenesis and improves cardiac repair post-MI by a mechanism involving the upregulation of SDF-1α/CXCR-4 and homing of vascular PCs.
authors: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA.
authors: Lanfang
authors: L
authors: Li
authors: Heng
authors: H
authors: Zeng
authors: Jian-Xiong
authors: JX
authors: Chen
mesh_terms: D000071916:AC133 Antigen; D054392:Adipokines; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000950:Antigens, Ly / Q000378:metabolism; D000073861:Apelin; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D006332:Cardiomegaly / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis; D006023:Glycoproteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism / Q000494:pharmacology*; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D000071656:Receptor, Notch3; D019718:Receptors, CXCR4 / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D020127:Recovery of Function; D012038:Regeneration / Q000187:drug effects*; D000072099:Serrate-Jagged Proteins; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000071916:AC133 Antigen; D054392:Adipokines; D015703:Antigens, CD; D000950:Antigens, Ly; D000073861:Apelin; C402826:Apln protein, mouse; D015415:Biomarkers; C514936:CXCR4 protein, mouse; D002135:Calcium-Binding Proteins; D002316:Cardiotonic Agents; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; C499373:Notch3 protein, mouse; D010455:Peptides; C000606024:Prom1 protein, mouse; D000071656:Receptor, Notch3; D019718:Receptors, CXCR4; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D042461:Vascular Endothelial Growth Factor A; C495199:apelin-13 peptide; C467480:vascular endothelial growth factor A, mouse; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D019009:Proto-Oncogene Proteins c-kit; D051057:Proto-Oncogene Proteins c-akt