KLF2 and KLF4 control endothelial identity and vascular integrity

• Text
• PDF

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 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.

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