Format

Send to

Choose Destination
See comment in PubMed Commons below
Arterioscler Thromb Vasc Biol. 2013 Nov;33(11):2608-17. doi: 10.1161/ATVBAHA.113.302161. Epub 2013 Aug 22.

The role of shear-induced transforming growth factor-β signaling in the endothelium.

Author information

1
From the Departments of Ophthalmology (T.E.W., N.G.d.P., P.A.D.) and Pathology (P.A.D.), Schepens Eye Research Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston; and La Jolla Bioengineering Institute, San Diego, CA (N.G.d.P.).

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 Krüppel-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 Krüppel-like factor 2 by shear.

CONCLUSIONS:

Shear stress of HUVECs induces TGF-β3 signaling and subsequent activation of Krüppel-like factor 2 and NO, and represents a novel role for TGF-β3 in the maintenance of HUVEC homeostasis in a hemodynamic environment.

KEYWORDS:

KLF2 protein, human; endothelium; hemodynamics; nitric oxide; transforming growth factor beta

PMID:
23968981
PMCID:
PMC4129450
DOI:
10.1161/ATVBAHA.113.302161
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center