title: Cardioprotective effects of adipokine apelin on myocardial infarction.
abstract: Angiogenesis plays an important role in myocardial infarction. Apelin and its natural receptor (angiotensin II receptor-like 1, AGTRL-1 or APLNR) induce sprouting of endothelial cells in an autocrine or paracrine manner. The aim of this study is to investigate whether apelin can improve the cardiac function after myocardial infarction by increasing angiogenesis in infarcted myocardium. Left ventricular end-diastolic pressure (LVEDP), left ventricular end systolic pressure (LVESP), left ventricular developed pressure (LVDP), maximal left ventricular pressure development (±LVdp/dtmax), infarct size, and angiogenesis were evaluated to analyze the cardioprotective effects of apelin on ischemic myocardium. Assays of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, 5-bromo-2'-deoxyuridine incorporation, wound healing, transwells, and tube formation were used to detect the effects of apelin on proliferation, migration, and chemotaxis of cardiac microvascular endothelial cells. Fluorescein isothiocyanate-labeled bovine serum albumin penetrating through monolayered cardiac microvascular endothelial cells was measured to evaluate the effects of apelin on permeability of microvascular endothelial cells. In vivo results showed that apelin increased ±LV dp/dtmax and LVESP values, decreased LVEDP values (all p < 0.05), and promoted angiogenesis in rat heart after ligation of the left anterior descending coronary artery. In vitro results showed that apelin dose-dependently enhanced proliferation, migration, chemotaxis, and tube formation, but not permeability of cardiac microvascular endothelial cells. Apelin also increased the expression of vascular endothelial growth factor receptors-2 (VEGFR2) and the endothelium-specific receptor tyrosine kinase (Tie-2) in cardiac microvascular endothelial cells. These results indicated that apelin played a protective role in myocardial infarction through promoting angiogenesis and decreasing permeability of microvascular endothelial cells via upregulating the expression of VEGFR2 and Tie-2 in cardiac microvascular endothelial cells.
authors.affiliation: The Department of Pathophysiology, Capital Medical University, Beijing, 100069, China.
authors.forename: Bao-Hai
authors.initials: BH
authors.lastname: Zhang
authors.forename: Cai-Xia
authors.initials: CX
authors.lastname: Guo
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Wang
authors.forename: Ling-Qiao
authors.initials: LQ
authors.lastname: Lu
authors.forename: Ya-Jie
authors.initials: YJ
authors.lastname: Wang
authors.forename: Li-Ke
authors.initials: LK
authors.lastname: Zhang
authors.forename: Feng-He
authors.initials: FH
authors.lastname: Du
authors.forename: Xiang-Jun
authors.initials: XJ
authors.lastname: Zeng
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D017208:Rats, Wistar; D042787:Receptor, TIE-2 / Q000187:drug effects / Q000378:metabolism; D020127:Recovery of Function; D013997:Time Factors; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000187:drug effects / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D043925:Angiogenesis Inducing Agents; D002316:Cardiotonic Agents; D036341:Intercellular Signaling Peptides and Proteins; C495199:apelin-13 peptide; D042787:Receptor, TIE-2; D040301:Vascular Endothelial Growth Factor Receptor-2