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Mesenchymal-endothelial transition contributes to cardiac neovascularization.

Publication Type : Journal Article

Publisher : Nature

Source : Nature, Volume 514, Issue 7524, p.585-90 (2014)

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Keywords : Animals, Cell Transdifferentiation, Coronary Vessels, Endothelial cells, female, Fibroblasts, In Vitro Techniques, male, Mesoderm, Mice, Myocardial Ischemia, Neovascularization, Physiologic, Tumor Suppressor Protein p53

Campus : Amritapuri

School : School of Biotechnology

Department : biotechnology

Year : 2014

Abstract : Endothelial cells contribute to a subset of cardiac fibroblasts by undergoing endothelial-to-mesenchymal transition, but whether cardiac fibroblasts can adopt an endothelial cell fate and directly contribute to neovascularization after cardiac injury is not known. Here, using genetic fate map techniques, we demonstrate that cardiac fibroblasts rapidly adopt an endothelial-cell-like phenotype after acute ischaemic cardiac injury. Fibroblast-derived endothelial cells exhibit anatomical and functional characteristics of native endothelial cells. We show that the transcription factor p53 regulates such a switch in cardiac fibroblast fate. Loss of p53 in cardiac fibroblasts severely decreases the formation of fibroblast-derived endothelial cells, reduces post-infarct vascular density and worsens cardiac function. Conversely, stimulation of the p53 pathway in cardiac fibroblasts augments mesenchymal-to-endothelial transition, enhances vascularity and improves cardiac function. These observations demonstrate that mesenchymal-to-endothelial transition contributes to neovascularization of the injured heart and represents a potential therapeutic target for enhancing cardiac repair.

Cite this Research Publication : Eric Ubil, Jinzhu Duan, Indulekha C. L. Pillai, Manuel Rosa-Garrido, Yong Wu, Francesca Bargiacchi, Yan Lu, Seta Stanbouly, Jie Huang, Mauricio Rojas, Thomas M Vondriska, Enrico Stefani, and Arjun Deb, “Mesenchymal-endothelial transition contributes to cardiac neovascularization.”, Nature, vol. 514, no. 7524, pp. 585-90, 2014.

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