TY - JOUR
T1 - KLF2 and KLF4 control endothelial identity and vascular integrity
AU - Sangwung, Panjamaporn
AU - Zhou, Guangjin
AU - Nayak, Lalitha
AU - Chan, E. Ricky
AU - Kumar, Sandeep
AU - Kang, Dong Won
AU - Zhang, Rongli
AU - Liao, Xudong
AU - Lu, Yuan
AU - Sugi, Keiki
AU - Fujioka, Hisashi
AU - Shi, Hong
AU - Lapping, Stephanie D.
AU - Ghosh, Chandra C.
AU - Higgins, Sarah J.
AU - Parikh, Samir M.
AU - Jo, Hanjoong
AU - Jain, Mukesh K.
N1 - Publisher Copyright:
© 2017 American Society for Clinical Investigation. All rights reserved.
PY - 2017/2/23
Y1 - 2017/2/23
N2 - Maintenance of vascular integrity in the adult animal is needed for survival, and it is critically dependent on the endothelial lining, which controls barrier function, blood fluidity, and flow dynamics. However, nodal regulators that coordinate endothelial identity and function in the adult animal remain poorly characterized. Here, we show that endothelial KLF2 and KLF4 control a large segment of the endothelial transcriptome, thereby affecting virtually all key endothelial functions. Inducible endothelial-specific deletion of Klf2 and/or Klf4 reveals that a single allele of either gene is sufficient for survival, but absence of both (EC-DKO) results in acute death from myocardial infarction, heart failure, and stroke. EC-DKO animals exhibit profound compromise in vascular integrity and profound dysregulation of the coagulation system. Collectively, these studies establish an absolute requirement for KLF2/4 for maintenance of endothelial and vascular integrity in the adult animal.
AB - Maintenance of vascular integrity in the adult animal is needed for survival, and it is critically dependent on the endothelial lining, which controls barrier function, blood fluidity, and flow dynamics. However, nodal regulators that coordinate endothelial identity and function in the adult animal remain poorly characterized. Here, we show that endothelial KLF2 and KLF4 control a large segment of the endothelial transcriptome, thereby affecting virtually all key endothelial functions. Inducible endothelial-specific deletion of Klf2 and/or Klf4 reveals that a single allele of either gene is sufficient for survival, but absence of both (EC-DKO) results in acute death from myocardial infarction, heart failure, and stroke. EC-DKO animals exhibit profound compromise in vascular integrity and profound dysregulation of the coagulation system. Collectively, these studies establish an absolute requirement for KLF2/4 for maintenance of endothelial and vascular integrity in the adult animal.
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U2 - 10.1172/jci.insight.91700
DO - 10.1172/jci.insight.91700
M3 - Article
AN - SCOPUS:85040507714
SN - 2379-3708
VL - 2
JO - JCI Insight
JF - JCI Insight
IS - 4
M1 - e91700
ER -