KLF2 and KLF4 Control Endothelial Identity and Vascular Integrity

Overview

Journal JCI Insight

Specialties Biomedical Engineering
General Medicine

Date 2017 Feb 28

PMID 28239661

Citations 123

Authors

Panjamaporn Sangwung

Guangjin Zhou

Lalitha Nayak

E Ricky Chan

Sandeep Kumar

Dong-Won Kang

Rongli Zhang

Xudong Liao

Yuan Lu

Keiki Sugi

Hisashi Fujioka

Hong Shi

Stephanie D Lapping

Chandra C Ghosh

Sarah J Higgins

Samir M Parikh

Hanjoong Jo

Mukesh K Jain

Affiliations

Soon will be listed here.

Abstract

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 and/or 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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