title: Endothelial cells overexpressing IL-8 receptor reduce cardiac remodeling and dysfunction following myocardial infarction.
abstract: The endothelium is a dynamic component of the cardiovascular system that plays an important role in health and disease. This study tested the hypothesis that targeted delivery of endothelial cells (ECs) overexpressing neutrophil membrane IL-8 receptors IL8RA and IL8RB reduces acute myocardial infarction (MI)-induced left ventricular (LV) remodeling and dysfunction and increases neovascularization in the area at risk surrounding the infarcted tissue. MI was created by ligating the left anterior descending coronary artery in 12-wk-old male Sprague-Dawley rats. Four groups of rats were studied: group 1: sham-operated rats without MI or EC transfusion; group 2: MI rats with intravenous vehicle; group 3: MI rats with transfused ECs transduced with empty adenoviral vector (Null-EC); and group 4: MI rats with transfused ECs overexpressing IL8RA/RB (1.5 × 10⁶ cells post-MI). Two weeks after MI, LV function was assessed by echocardiography; infarct size was assessed by triphenyltetrazolium chloride (live tissue) and picrosirus red (collagen) staining, and capillary density and neutrophil infiltration in the area at risk were measured by CD31 and MPO immunohistochemical staining, respectively. When compared with the MI + vehicle and MI-Null-EC groups, transfusion of IL8RA/RB-ECs decreased neutrophil infiltration and pro-inflammatory cytokine expression and increased capillary density in the area at risk, decreased infarct size, and reduced MI-induced LV dysfunction. These findings provide proof of principle that targeted delivery of ECs is effective in repairing injured cardiac tissue. Targeted delivery of ECs to infarcted hearts provides a potential novel strategy for the treatment of acute MI in humans.
authors.affiliation: Vascular Biology and Hypertension Program, Division of Cardiovascular Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama;
authors.forename: Xiangmin
authors.initials: X
authors.lastname: Zhao
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Dongqi
authors.initials: D
authors.lastname: Xing
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Jinyan
authors.initials: J
authors.lastname: Fu
authors.forename: Kaizheng
authors.initials: K
authors.lastname: Gong
authors.forename: Fadi G
authors.initials: FG
authors.lastname: Hage
authors.forename: Suzanne
authors.initials: S
authors.lastname: Oparil
authors.forename: Yiu-Fai
authors.initials: YF
authors.lastname: Chen
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018919:Neovascularization, Physiologic; D020556:Neutrophil Infiltration; D051381:Rats; D017207:Rats, Sprague-Dawley; D053700:Receptors, Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013997:Time Factors; D014161:Transduction, Genetic; D014162:Transfection; D015854:Up-Regulation; D018487:Ventricular Dysfunction, Left / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: D018836:Inflammation Mediators; D053700:Receptors, Interleukin-8; D011993:Recombinant Fusion Proteins
keywords: cell therapy; endothelial cells; interleukin-8 receptors; myocardial infarction; neovascularization