Artery Research

Volume 6, Issue 4, December 2012, Pages 178 - 179

P3.06 CYCLIC STRETCH-INDUCED THROMBIN GENERATION BY RAT VASCULAR SMOOTH MUSCLE CELLS IS MEDIATED BY THE INTEGRIN (V(3) SIGNALING PATHWAY)

Authors
H. Louis1, 2, Z. Li2, M. Bourhim1, 2, V. Regnault1, 2, P. Lacolley1, 2
1Université de Lorraine, Nancy, France
2Inserm U961, Nancy, France
Available Online 17 November 2012.
DOI
10.1016/j.artres.2012.09.133How to use a DOI?
Open Access
This is an open access article distributed under the CC BY-NC license.

Vascular smooth muscle cell (VSMC) phenotypic modulation plays a pivotal role in atherothrombotic diseases. Thrombin generation at the surface of VSMCs and activation of integrin mechanotransduction pathways represent potential mechanisms. Here, we examine whether mechanical stretch increases thrombin generation on cultured rat aortic VSMCs.

We used a model of cultured rat aortic VSMCs submitted to cyclic stretch (Flexcell, 10% at 1 Hz). Cyclic stretch during 60 and 360 minutes induced a differentiated contractile VSMC phenotype without apoptosis and up-regulated integrin αvβ3 expression 1.3 fold. Cyclic stretch stimulated binding of prothrombin to VSMCs and increased the subsequent thrombin generation by 67% and 30% respectively. It also produced time-dependent phosphorylation of Src, FAK and Akt as well as increased ILK phosphorylation at 15 minutes. Talin cleavage was increased between 5 and 60 minutes. The αvβ3 antagonist cRGDPV and αv-siRNA blocked these responses. A talin-siRNA decreased stretch-induced αv expression and the phosphorylation of Src, FAK, Akt and ILK. ILK-siRNA had no effect on αv expression but inhibited phosphorylation of Akt and talin at 360 minutes.

These results demonstrate that cyclic stretch stimulates the generation of thrombin on rat VSMCs via activation of integrin αvβ3 pathways. They further suggest that intravascular generation of thrombin may be regulated by integrin αvβ3 antagonists in patients with high pulse pressure.

Journal
Artery Research
Volume-Issue
6 - 4
Pages
178 - 179
Publication Date
2012/11/17
ISSN (Online)
1876-4401
ISSN (Print)
1872-9312
DOI
10.1016/j.artres.2012.09.133How to use a DOI?
Open Access
This is an open access article distributed under the CC BY-NC license.

Cite this article

TY  - JOUR
AU  - H. Louis
AU  - Z. Li
AU  - M. Bourhim
AU  - V. Regnault
AU  - P. Lacolley
PY  - 2012
DA  - 2012/11/17
TI  - P3.06 CYCLIC STRETCH-INDUCED THROMBIN GENERATION BY RAT VASCULAR SMOOTH MUSCLE CELLS IS MEDIATED BY THE INTEGRIN (V(3) SIGNALING PATHWAY)
JO  - Artery Research
SP  - 178
EP  - 179
VL  - 6
IS  - 4
SN  - 1876-4401
UR  - https://doi.org/10.1016/j.artres.2012.09.133
DO  - 10.1016/j.artres.2012.09.133
ID  - Louis2012
ER  -