Shear stress regulation of Krüppel-like factor 2 expression is flow pattern-specific.
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.
Wang
Nanping
N
Department of Bioengineering, Whitaker Institute of Biomedical Engineering, University of California-San Diego, La Jolla, CA 92093-0412, USA.
Miao
Hui
H
Li
Yi-Shuan
YS
Zhang
Peng
P
Haga
Jason H
JH
Hu
Yingli
Y
Young
Angela
A
Yuan
Suli
S
Nguyen
Phu
P
Wu
Chia-Ching
CC
Chien
Shu
S
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
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