title: Overexpression of angiopoietin-1 increases CD133+/c-kit+ cells and reduces myocardial apoptosis in db/db mouse infarcted hearts.
abstract: Hematopoietic progenitor CD133(+)/c-kit(+) cells have been shown to be involved in myocardial healing following myocardial infarction (MI). Previously we demonstrated that angiopoietin-1(Ang-1) is beneficial in the repair of diabetic infarcted hearts. We now investigate whether Ang-1 affects CD133(+)/c-kit(+) cell recruitment to the infarcted myocardium thereby mediating cardiac repair in type II (db/db) diabetic mice. db/db mice were administered either adenovirus Ang-1 (Ad-Ang-1) or Ad-β-gal systemically immediately after ligation of the left anterior descending coronary artery (LAD). Overexpression of Ang-1 resulted in a significant increase in CXCR-4/SDF-1α expression and promoted CD133(+)/c-kit(+), CD133(+)/CXCR-4(+) and CD133(+)/SDF-1α(+) cell recruitment into ischemic hearts. Overexpression of Ang-1 led to significant increases in number of CD31(+) and smooth muscle-like cells and VEGF expression in bone marrow (BM). This was accompanied by significant decreases in cardiac apoptosis and fibrosis and an increase in myocardial capillary density. Ang-1 also upregulated Jagged-1, Notch3 and apelin expression followed by increases in arteriole formation in the infarcted myocardium. Furthermore, overexpression of Ang-1 resulted in a significant improvement of cardiac functional recovery after 14 days of ischemia. Our data strongly suggest that Ang-1 attenuates cardiac apoptosis and promotes cardiac repair by a mechanism involving in promoting CD133(+)/c-kit(+) cells and angiogenesis in diabetic db/db mouse infarcted hearts.
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi, USA.
authors.forename: Heng
authors.initials: H
authors.lastname: Zeng
authors.forename: Lanfang
authors.initials: L
authors.lastname: Li
authors.forename: Jian-Xiong
authors.initials: JX
authors.lastname: Chen
mesh_terms: D000071916:AC133 Antigen; D000199:Actins / Q000378:metabolism; D054392:Adipokines; D042683:Angiopoietin-1 / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000073861:Apelin; D017209:Apoptosis; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002196:Capillaries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006332:Cardiomegaly / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004719:Endomyocardial Fibrosis / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006023:Glycoproteins / Q000378:metabolism*; D006334:Heart Function Tests; D006412:Hematopoietic Stem Cells / Q000166:cytology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009203:Myocardial Infarction / Q000150:complications / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D010455:Peptides / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D000071656:Receptor, Notch3; D019718:Receptors, CXCR4 / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D000071916:AC133 Antigen; D000199:Actins; D054392:Adipokines; D042683:Angiopoietin-1; D015703:Antigens, CD; D000073861:Apelin; C402826:Apln protein, mouse; D002135:Calcium-Binding Proteins; D054377:Chemokine CXCL12; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C499373:Notch3 protein, mouse; D010455:Peptides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C000606024:Prom1 protein, mouse; D000071656:Receptor, Notch3; D019718:Receptors, CXCR4; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; C544013:alpha-smooth muscle actin, mouse; D019009:Proto-Oncogene Proteins c-kit