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.
Subject(s)
Animals , Mice , Cell Transplantation , Endothelial Cells/cytology , Homeodomain Proteins/genetics , Immunohistochemistry , Lymphangiogenesis/genetics , Mice, Inbred C57BL , Mice, Transgenic , Myocardial Infarction/metabolism , Real-Time Polymerase Chain Reaction , Stem Cell Transplantation , Tumor Suppressor Proteins/genetics , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor D/geneticsABSTRACT
PURPOSE: The morphologic characteristics and adhesion complex formation of cultured limbal epithelium of rabbit on amniotic membrane, in vitro and in vivo. METHODS: Rabbit limbal explants were cultured in vitro on amniotic membrane for 4 weeks. In the in vivo culture, the rabbit corneal epithelium was removed. Next, a tunnel was created at the limbus and, the edge of amniotic membrane was secured in the tunnel and cultured for 4 weeks. The proliferation of epithelium on the amniotic membrane was observed for 4 weeks at 1 week intervals. RESULTS: AE-5 immunohistochemical staining was positive and PAS staining was negative for cultured rabbit limbal epithelium, in vitro and in vivo. Hematoxylin and Eosin staining showed the morphologic characteristics of normal rabbit corneal epithelium in both groups. Transmission electron microscopy performed at an interval of 1 week showed adhesion complex by 3 weeks of in vitro culture, and no significant change was seen until week 4. The formation of the adhesion complex was shown starting at week 1 of in vivo culture and increased until week 4. CONCLUSIONS: The morphology of corneal limbal epithelium of rabbits cultured on amniotic membrane in vitro and in vivo, did not differ significantly compared with normal rabbit epithelium. In vivo culture resulted in more a normal-looking adhesion complex compared with the in vitro culture.