ABSTRACT
CD146 is a newly identified endothelial biomarker that has been implicated in angiogenesis. Though in vitro angiogenic function of CD146 has been extensively reported, in vivo evidence is still lacking. To address this issue, we generated endothelial-specific CD146 knockout (CD146(EC-KO)) mice using the Tg(Tek-cre) system. Surprisingly, these mice did not exhibit any apparent morphological defects in the development of normal retinal vasculature. To evaluate the role of CD146 in pathological angiogenesis, a xenograft tumor model was used. We found that both tumor volume and vascular density were significantly lower in CD146(EC-KO) mice when compared to WT littermates. Additionally, the ability for sprouting, migration and tube formation in response to VEGF treatment was impaired in endothelial cells (ECs) of CD146(EC-KO) mice. Mechanistic studies further confirmed that VEGF-induced VEGFR-2 phosphorylation and AKT/p38 MAPKs/NF-κB activation were inhibited in these CD146-null ECs, which might present the underlying cause for the observed inhibition of tumor angiogenesis in CD146(EC-KO) mice. These results suggest that CD146 plays a redundant role in physiological angiogenic processes, but becomes essential during pathological angiogenesis as observed in tumorigenesis.
Subject(s)
Animals , Female , Male , Mice , CD146 Antigen , Genetics , Metabolism , Cells, Cultured , Endothelial Cells , Cell Biology , Metabolism , Fibrosarcoma , Metabolism , Pathology , Melanoma, Experimental , Metabolism , Pathology , Mice, Inbred C57BL , Mice, Knockout , NF-kappa B , Metabolism , Neovascularization, Physiologic , Phosphorylation , Proto-Oncogene Proteins c-akt , Metabolism , Retinal Vein , Pathology , Signal Transduction , Transplantation, Homologous , Vascular Endothelial Growth Factor A , Pharmacology , Vascular Endothelial Growth Factor Receptor-2 , MetabolismABSTRACT
Objective To investigate the correlation between the expression of adhesion molecule CD146 and the vulnerability of carotid atherosclerotic plaque.Methods The plaque samples were collected from 40 patients who underwent the carotid endarterectomy and were divided into the stable plaque group and the instable plaque group by ultrasound imaging.Five carotid artery samples were taken from the healthy donors as the control.Immunohistochemistry was applied to test the CD146 expression in all samples.Results Higher expression of CD146 was observed in the atherosclerotic plaques than in the healthy control.Moreover,statistical difference was found in the expression of CD146 in the plaques between the instable plaque group and the stable plaque group (0.31 ± 0.19 vs 0.17 ± 0.07,P ＜ 0.05).The expression of CD146 was positively correlated with the necrotic area (r =0.471 8,P =0.019 9) and the matrix metalloproteinase (MMP)-9 expression in the plaques (r =0.535 6,P =0.000 9).Conclusion The CD146 expression is correlated with the vulnerability of carotid atherosclerotic plaque.