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Mesenchymal-endothelial transition contributes to cardiac neovascularization
#MMPMID25317562
Ubil E
; Duan J
; Pillai IC
; Rosa-Garrido M
; Wu Y
; Bargiacchi F
; Lu Y
; Stanbouly S
; Huang J
; Rojas M
; Vondriska TM
; Stefani E
; Deb A
Nature
2014[Oct]; 514
(7524
): 585-90
PMID25317562
show ga
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.
|*Cell Transdifferentiation
[MESH]
|*Neovascularization, Physiologic
[MESH]
|Animals
[MESH]
|Coronary Vessels/*cytology/*growth & development
[MESH]
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