Background : The lymphatic system is involved in fluid homeostasis of the cardiac interstitium. Lymphangiogenesis in myocardial remodeling after myocardial infarction(MI) has not previously been examined. Bone marrow(BM)-derived cells have been shown to contribute neovascularization in various ischemic cardiovascular diseases. We sought to investigate whether BM-derives cells contribute in lymphatic distribution in the process of myocardial remodelling after MI.
Methods and Results: We made mice (C57bl/6J) MI by ligation of left anterior descending coronary artery. Real-time RT-PCR with 2/4 week myocardial tissue samples revealed lymphangiogenetic cytokines expressed significantly higher level of VEGF C (11.1 fold, P < 0.01), Lyve-1 (6.1 fold, P < 0.01), phodoplanin (2.3 fold, P < 0.05), Prox-1 (15 fold, P < 0.01) compared to control groups. To trace the BM-derived cells, we performed BM transplantation with GFP reporter cells. At least four weeks later BMT, we made MI in BMT mice. Two and four weeks later, we counted GFP positive cells incorporated into lymphatics in myocardium and also performed immunohistochemistry to identify the fate of the incorporated cells. Lymphatic vessels were not detected in lesions with necrosis/infarction area, and newly formed lymphatics appeared in the peri-infarction area. Some of GFP positive BM-derived cells contribute to newly formed lymphatics.
Conclusions: Lymphangiogenic markers increased in a mouse model of MI. BM-derived cells contribute to newly formed lymphatic vessels in peri-infarction area. These novel findings suggest that newly formed lymphatic vessels may be involved in myocardial remodelling after MI.