title: Endothelial progenitor cell transplantation decreases lymphangiogenesis and adverse myocardial remodeling in a mouse model of acute myocardial infarction.
abstract: Cardiac lymphatic system in the remodeling after acute myocardial infarction (AMI) has been overlooked. We wanted to investigate the role of bone marrow-derived endothelial progenitor cells (EPCs) and their contribution to lymphatic distribution in myocardial remodeling after AMI. Mouse (C57bl/6J) MI models were created by ligation of the left anterior descending coronary artery and were treated with phosphate buffered saline (PBS) or EPCs. Real-time RT-PCR with 2- to 4-week myocardial tissue samples revealed that lymphangiogenetic factors such as vascular endothelial growth factor (VEGF)-C (8.5 fold, P < 0.05), VEGF-D (6.1 fold, P < 0.05), Lyve-1 (15 fold, P < 0.05), and Prox-1 (11 fold, P < 0.05) were expressed at significantly higher levels in the PBS group than the EPC group. The PBS group also showed a significantly higher density of lymphatic vessels in the peri-infarction area. Echocardiography showed that from 2 weeks after the treatment, left ventricle (LV) dimensions at both systole and diastole were significantly smaller in the EPC group than in the PBS group (P < 0.01) and LV fractional shortening was higher in the EPC group accordingly (P < 0.01). Lymphangiogenic markers increased in a mouse MI model. EPC transplantation decreased lymphangiogenesis and adverse ventricular remodeling after AMI. These novel findings suggest that new lymphatic vessels may be formed in severely damaged myocardium, and may be involved in adverse myocardial remodeling after AMI.
authors.affiliation: Division of Cardiology, Chungnam National University, Daejeon 301-721, Korea.
authors.forename: Jae-Hyeong
authors.initials: JH
authors.lastname: Park
authors.forename: Jung Yeon
authors.initials: JY
authors.lastname: Yoon
authors.forename: Seon Mi
authors.initials: SM
authors.lastname: Ko
authors.forename: Seon Ah
authors.initials: SA
authors.lastname: Jin
authors.forename: Jun Hyung
authors.initials: JH
authors.lastname: Kim
authors.forename: Chung-Hyun
authors.initials: CH
authors.lastname: Cho
authors.forename: Jin-Man
authors.initials: JM
authors.lastname: Kim
authors.forename: Jae-Hwan
authors.initials: JH
authors.lastname: Lee
authors.forename: Si Wan
authors.initials: SW
authors.lastname: Choi
authors.forename: In-Whan
authors.initials: IW
authors.lastname: Seong
authors.forename: Jin Ok
authors.initials: JO
authors.lastname: Jeong
mesh_terms: D000818:Animals; D017690:Cell Transplantation; D042783:Endothelial Cells / Q000166:cytology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D042583:Lymphangiogenesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D060888:Real-Time Polymerase Chain Reaction; D033581:Stem Cell Transplantation; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D042643:Vascular Endothelial Growth Factor D / Q000235:genetics / Q000378:metabolism; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D018398:Homeodomain Proteins; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; D042643:Vascular Endothelial Growth Factor D; D000098551:Prospero-Related Homeobox 1 Protein