P11 The Role of Smooth Muscle Integrin Alpha V and TGF-Beta Pathways in Vascular Fibrosis

DOI

10.2991/artres.k.191224.046How to use a DOI?

Abstract

It has been demonstrated that arterial stiffness is linked to arterial fibrosis manifested by increased collagen and other extracellular matrix synthesis in smooth muscle cells (SMC). Transmembrane receptors integrins mediating cell-cell and cell-matrix signalling pathways are involved in tissue fibrosis. We study the role of one integrin subunit av in angiotensin II (AngII)-induced SMC proliferation and arterial fibrosis and stiffness using SMC specific knock-out av mouse model (avSMKO) induced in adult mice by injection of tamoxifen. There is no difference in vascular fibrosis in basal conditions between control and mutant mice. However, decreased arterial fibrosis is observed in avSMKO mutant mice after 28-day perfusion of AngII. Analysis of RNA from aorta of control and mutant mice by Affymetrix microarrays indicated an alteration of the TGF-β pathway in AngII-treated mutant mice. In order to examine the mechanism associated to the decreased fibrosis in vascular SMC from avSMKO mice, isolated VSMC from the aorta of control and avSMKO mice were treated with TGF-β1 or AngII. The results indicated that these two treatments increased the expression of collagen, fibronectin and integrin αν at the protein and RNA levels as well as the phosphorylation of ERK and smad2/3 in the control cells. Inactivation of integrin αν partly inhibited all above effects induced by TGF-β1 and AngII. Our study indicates a role of av and TGF-β1 in the arterial fibrogenesis. Therefore, av signaling could be a therapeutic target against arterial fibrosis and stiffness in pathological conditions.

Copyright

© 2019 Association for Research into Arterial Structure and Physiology. Publishing services by Atlantis Press International B.V.

Open Access

This is an open access article distributed under the CC BY-NC 4.0 license (http://creativecommons.org/licenses/by-nc/4.0/).

TY  - JOUR
AU  - Alexandre Raoul
AU  - Ekaterina Belozertseva
AU  - Huguette Louis
AU  - Zhenlin Li
AU  - Veronique Regnault
AU  - Patrick Lacolley
PY  - 2020
DA  - 2020/02/15
TI  - P11 The Role of Smooth Muscle Integrin Alpha V and TGF-Beta Pathways in Vascular Fibrosis
JO  - Artery Research
SP  - S54
EP  - S54
VL  - 25
IS  - Supplement 1
SN  - 1876-4401
UR  - https://doi.org/10.2991/artres.k.191224.046
DO  - 10.2991/artres.k.191224.046
ID  - Raoul2020
ER  -