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2015 ; 5
(ä): 16193
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Venous Endothelial Marker COUP-TFII Regulates the Distinct Pathologic Potentials
of Adult Arteries and Veins
#MMPMID26537113
Cui X
; Lu YW
; Lee V
; Kim D
; Dorsey T
; Wang Q
; Lee Y
; Vincent P
; Schwarz J
; Dai G
Sci Rep
2015[Nov]; 5
(ä): 16193
PMID26537113
show ga
Arteries and veins have very different susceptibility to certain vascular
diseases such as atherosclerosis and vascular calcification. The molecular
mechanisms of these differences are not fully understood. In this study, we
discovered that COUP-TFII, a transcription factor critical for establishing the
venous identity during embryonic vascular development, also regulates the
pathophysiological functions of adult blood vessels, especially those directly
related to vascular diseases. Specifically, we found that suppression of
COUP-TFII in venous ECs switched its phenotype toward pro-atherogenic by
up-regulating the expression of inflammatory genes and down-regulating
anti-thrombotic genes. ECs with COUP-TFII knockdown also readily undergo
endothelial-to-mesenchymal transition (EndoMT) and subsequent osteogenic
differentiation with dramatically increased osteogenic transcriptional program
and calcium deposition. Consistently, over-expression of COUP-TFII led to the
completely opposite effects. In vivo validation of these pro-atherogenic and
osteogenic genes also demonstrates a broad consistent differential expression
pattern in mouse aorta vs. vena cava ECs, which cannot be explained by the
difference in hemodynamic flow. These data reveal phenotypic modulation by
different levels of COUP-TFII in arterial and venous ECs, and suggest COUP-TFII
may play an important role in the different susceptibilities of arteries and
veins to vascular diseases such as atherosclerosis and vascular calcification.