Exp Mol Med.  2011 Aug;43(8):479-485. 10.3858/emm.2011.43.8.054.

Endothelial progenitor cell transplantation decreases lymphangiogenesis and adverse myocardial remodeling in a mouse model of acute myocardial infarction

• Park JH
• Yoon JY
• Ko SM
• Jin SA
• Kim JH
• Cho CH
• Kim JM
• Lee JH
• Choi SW
• Seong IW
• Jeong JO

• KMID: 1022123
• DOI: http://doi.org/10.3858/emm.2011.43.8.054

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.

Keyword

endothelial cells; lymphangiogenesis; myocardial infarction; stem cells; ventricular remodeling

MeSH Terms

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