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@ARTICLE{Zhang:179730,
author = {C. Zhang and H. He and J. Dai and Y. Li and J. He and W.
Yang and J. Dai and F. Han and W. Kong and X. Wang and X.
Zheng and J. Zhou and W. Pan and Z. Chen and S. Mahak$^*$
and Y. Zhang and F. Guo and J. Hu},
title = {{KANK}4 {P}romotes {A}rteriogenesis by {P}otentiating
{VEGFR}2 {S}ignaling in a {TALIN}-1-{D}ependent {M}anner.},
journal = {Arteriosclerosis, thrombosis, and vascular biology},
volume = {42},
number = {6},
issn = {0276-5047},
address = {Stanford, Calif.},
publisher = {HighWire},
reportid = {DKFZ-2022-00862},
pages = {772-788},
year = {2022},
note = {2022 Jun;42(6):772-788 / DKFZ-ZMBH Alliance},
abstract = {Arteriogenesis plays a critical role in maintaining
adequate tissue blood supply and is related to a favorable
prognosis in arterial occlusive diseases. Strategies aimed
at promoting arteriogenesis have thus far not been
successful because the factors involved in arteriogenesis
remain incompletely understood. Previous studies suggest
that evolutionarily conserved KANK4 (KN motif and ankyrin
repeat domain-containing proteins 4) might involve in
vertebrate vessel development. However, how the KANK4
regulates vessel function remains unknown. We aim to
determine the role of endothelial cell-specifically
expressed KANK4 in arteriogenesis.The role of KANK4 in
regulating arteriogenesis was evaluated using Kank4-/- and
KANK4iECOE mice. Molecular mechanisms underlying
KANK4-potentiated arteriogenesis were investigated by
employing RNA transcriptomic profiling and mass spectrometry
analysis.By analyzing Kank4-EGFP reporter mice, we showed
that KANK4 was specifically expressed in endothelial cells.
In particular, KANK4 displayed a dynamic expression pattern
from being ubiquitously expressed in all endothelial cells
of the developing vasculature to being explicitly expressed
in the endothelial cells of arterioles and arteries in
matured vessels. In vitro microfluidic chip-based vascular
morphology analysis and in vivo hindlimb ischemia assays
using Kank4-/- and KANK4iECOE mice demonstrated that
deletion of KANK4 impaired collateral artery growth and the
recovery of blood perfusion, whereas KANK4 overexpression
leads to increased vessel caliber and blood perfusion. Bulk
RNA sequencing and Co-immunoprecipitation/mass spectrometry
(Co-IP/MS) analysis identified that KANK4 promoted EC
proliferation and collateral artery remodeling through
coupling VEGFR2 (vascular endothelial growth factor receptor
2) to TALIN-1, which augmented the activation of the VEGFR2
signaling cascade.This study reveals a novel role for KANK4
in arteriogenesis in response to ischemia. KANK4 links
VEGFR2 to TALIN-1, resulting in enhanced VEGFR2 activation
and increased EC proliferation, highlighting that KANK4 is a
potential therapeutic target for promoting arteriogenesis
for arterial occlusive diseases.},
keywords = {arteriole (Other) / endothelial cell (Other) / hind limb
(Other) / mice (Other) / perfusion (Other)},
cin = {A190},
ddc = {610},
cid = {I:(DE-He78)A190-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35477278},
doi = {10.1161/ATVBAHA.122.317711},
url = {https://inrepo02.dkfz.de/record/179730},
}