title: KLF2 and KLF4 control endothelial identity and vascular integrity.
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 ofKlf2and/orKlf4reveals 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.affiliation: Cardiovascular Research Institute, Department of Medicine, and.|Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors.forename: Panjamaporn
authors.initials: P
authors.lastname: Sangwung
authors.affiliation: Cardiovascular Research Institute, Department of Medicine, and.
authors.forename: Guangjin
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Cardiovascular Research Institute, Department of Medicine, and.|Division of Hematology and Oncology, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Lalitha
authors.initials: L
authors.lastname: Nayak
authors.affiliation: Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors.forename: E Ricky
authors.initials: ER
authors.lastname: Chan
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA.
authors.forename: Dong-Won
authors.initials: DW
authors.lastname: Kang
authors.affiliation: Cardiovascular Research Institute, Department of Medicine, and.
authors.forename: Rongli
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Cardiovascular Research Institute, Department of Medicine, and.
authors.forename: Xudong
authors.initials: X
authors.lastname: Liao
authors.affiliation: Cardiovascular Research Institute, Department of Medicine, and.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Cardiovascular Research Institute, Department of Medicine, and.
authors.forename: Keiki
authors.initials: K
authors.lastname: Sugi
authors.affiliation: Electron Microscopy Core Facility, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Fujioka
authors.affiliation: Cardiovascular Research Institute, Department of Medicine, and.
authors.forename: Hong
authors.initials: H
authors.lastname: Shi
authors.affiliation: Cardiovascular Research Institute, Department of Medicine, and.
authors.forename: Stephanie D
authors.initials: SD
authors.lastname: Lapping
authors.affiliation: Center for Vascular Biology Research and Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Chandra C
authors.initials: CC
authors.lastname: Ghosh
authors.affiliation: Center for Vascular Biology Research and Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Higgins
authors.affiliation: Center for Vascular Biology Research and Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Samir M
authors.initials: SM
authors.lastname: Parikh
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA.|Division of Cardiology, Emory University, Atlanta, Georgia, USA.
authors.forename: Hanjoong
authors.initials: H
authors.lastname: Jo
authors.affiliation: Cardiovascular Research Institute, Department of Medicine, and.|Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.|Harrington Heart and Vascular Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.
authors.forename: Mukesh K
authors.initials: MK
authors.lastname: Jain
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000235:genetics*; D001778:Blood Coagulation Disorders / Q000235:genetics; D002199:Capillary Permeability / Q000235:genetics*; D004730:Endothelium, Vascular / Q000378:metabolism*; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000235:genetics; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000235:genetics; D020521:Stroke / Q000235:genetics
chemical_list: C498314:Klf2 protein, mouse; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors