@article {1363218,
	title = {The role of shear-induced transforming growth factor-β signaling in the endothelium},
	journal = {Arterioscler Thromb Vasc Biol},
	volume = {33},
	number = {11},
	year = {2013},
	month = {2013 Nov},
	pages = {2608-17},
	abstract = {OBJECTIVE: Vascular endothelial cells (ECs) are continuously exposed to blood flow that contributes to the maintenance of vessel structure and function; however, the effect of hemodynamic forces on transforming growth factor-β (TGF-β) signaling in the endothelium is poorly described. We examined the potential role of TGF-β signaling in mediating the protective effects of shear stress on ECs. APPROACH AND RESULTS: Human umbilical vein ECs (HUVECs) exposed to shear stress were compared with cells grown under static conditions. Signaling through the TGF-β receptor ALK5 was inhibited with SB525334. Cells were examined for morphological changes and harvested for analysis by real-time polymerase chain reaction, Western blot analysis, apoptosis, proliferation, and immunocytochemistry. Shear stress resulted in ALK5-dependent alignment of HUVECs as well as attenuation of apoptosis and proliferation compared with static controls. Shear stress led to an ALK5-dependent increase in TGF-β3 and Kr{\"u}ppel-like factor 2, phosphorylation of endothelial NO synthase, and NO release. Addition of the NO donor S-nitroso-N-acetylpenicillamine rescued the cells from apoptosis attributable to ALK5 inhibition under shear stress. Knockdown of TGF-β3, but not TGF-β1, disrupted the HUVEC monolayer and prevented the induction of Kr{\"u}ppel-like factor 2 by shear. CONCLUSIONS: Shear stress of HUVECs induces TGF-β3 signaling and subsequent activation of Kr{\"u}ppel-like factor 2 and NO, and represents a novel role for TGF-β3 in the maintenance of HUVEC homeostasis in a hemodynamic environment.},
	keywords = {Apoptosis, Endothelium, Vascular, Hemodynamics, Human Umbilical Vein Endothelial Cells, Humans, Imidazoles, Kruppel-Like Transcription Factors, Nitric Oxide, Protein-Serine-Threonine Kinases, Quinoxalines, Receptors, Transforming Growth Factor beta, RNA, Messenger, Signal Transduction, Stress, Mechanical, Transforming Growth Factor beta3},
	issn = {1524-4636},
	doi = {10.1161/ATVBAHA.113.302161},
	author = {Walshe, Tony E and Dela Paz, Nathaniel G and D{\textquoteright}Amore, Patricia A}
}
