Endothelial progenitor cell transplantation decreases lymphangiogenesis and adverse myocardial remodeling in a mouse model of acute myocardial infarction.
10.3858/emm.2011.43.8.054
- Author:
Jae Hyeong PARK
1
;
Jung Yeon YOON
;
Seon Mi KO
;
Seon Ah JIN
;
Jun Hyung KIM
;
Chung Hyun CHO
;
Jin Man KIM
;
Jae Hwan LEE
;
Si Wan CHOI
;
In Whan SEONG
;
Jin Ok JEONG
Author Information
1. Division of Cardiology, Department of Internal Medicine, School of Medicine, Chungnam National University, Daejeon 301-721, Korea. jojeong@cnu.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
endothelial cells;
lymphangiogenesis;
myocardial infarction;
stem cells;
ventricular remodeling
- MeSH:
Animals;
Cell Transplantation;
Endothelial Cells/*cytology;
Homeodomain Proteins/genetics/metabolism;
Immunohistochemistry;
Lymphangiogenesis/genetics/*physiology;
Mice;
Mice, Inbred C57BL;
Mice, Transgenic;
Myocardial Infarction/metabolism/physiopathology/*therapy;
Real-Time Polymerase Chain Reaction;
*Stem Cell Transplantation;
Tumor Suppressor Proteins/genetics/metabolism;
Vascular Endothelial Growth Factor A/genetics/metabolism;
Vascular Endothelial Growth Factor D/genetics/metabolism
- From:Experimental & Molecular Medicine
2011;43(8):479-485
- CountryRepublic of Korea
- Language:English
-
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.
