title: Shear stress regulation of Krüppel-like factor 2 expression is flow pattern-specific.
abstract: Flow patterns in blood vessels contribute to focal distribution of atherosclerosis; the underlying mechanotransduction pathways remain to be investigated. We demonstrate that different flow patterns elicit distinct responses of Krüppel-like factor-2 (KLF2) in endothelial cells (ECs) in vitro and in vivo. While pulsatile flow with a significant forward direction induced sustained expression of KLF2 in cultured ECs, oscillatory flow with little forward direction caused prolonged suppression after a transient induction. The suppressive effect of oscillatory flow was Src-dependent. Immunohistochemical studies on ECs at arterial branch points revealed that KLF2 protein levels were related to local hemodynamics. Such flow-associated expression patterns were also demonstrated in a rat aortic restenosis model. Inhibition of KLF2 with siRNA sensitized ECs to oxidized LDL-induced apoptosis, indicating a protective role of KLF2. In conclusion, differential regulation of KLF2 may mediate the distinct vascular effects induced by various patterns of shear stress.
authors.affiliation: Department of Bioengineering, Whitaker Institute of Biomedical Engineering, University of California-San Diego, La Jolla, CA 92093-0412, USA.
authors.forename: Nanping
authors.initials: N
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Miao
authors.forename: Yi-Shuan
authors.initials: YS
authors.lastname: Li
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.forename: Jason H
authors.initials: JH
authors.lastname: Haga
authors.forename: Yingli
authors.initials: Y
authors.lastname: Hu
authors.forename: Angela
authors.initials: A
authors.lastname: Young
authors.forename: Suli
authors.initials: S
authors.lastname: Yuan
authors.forename: Phu
authors.initials: P
authors.lastname: Nguyen
authors.forename: Chia-Ching
authors.initials: CC
authors.lastname: Wu
authors.forename: Shu
authors.initials: S
authors.lastname: Chien
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000502:physiology; D001024:Aortic Valve Stenosis / Q000503:physiopathology; D017209:Apoptosis / Q000187:drug effects; D002445:Celiac Artery / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology* / Q000502:physiology*; D005786:Gene Expression Regulation; D006439:Hemodynamics; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis* / Q000172:deficiency; D008297:Male; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D014471:Umbilical Veins; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: C108123:4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine; C096161:KLF2 protein, human; D051741:Kruppel-Like Transcription Factors; D011720:Pyrazoles; D011743:Pyrimidines; D019061:src-Family Kinases