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JCI Insight. 2017 Feb 23;2(4):e91700. doi: 10.1172/jci.insight.91700.

KLF2 and KLF4 control endothelial identity and vascular integrity.

Author information

1
Cardiovascular Research Institute, Department of Medicine, and.
2
Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
3
Division of Hematology and Oncology, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, Ohio, USA.
4
Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
5
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA.
6
Electron Microscopy Core Facility, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
7
Center for Vascular Biology Research and Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
8
Division of Cardiology, Emory University, Atlanta, Georgia, USA.
9
Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.

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.

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