Artery Research

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Volume 16, Issue C, December 2016, Pages 54 - 55

4.4 ARTERIAL PHENOTYPE MODULATION AND REGULATION OF VASCULAR FIBROSIS IN MICE BY CONDITIONAL INACTIVATION OF INTEGRIN AV SUBUNIT IN VASCULAR SMOOTH MUSCLE CELLS

Authors
Ekaterina Belozertseva1, Huguette Louis1, Zhenlin Li2, Mustapha Bourhim1, Dominique Dumas3, Veronique Regnault1, Patrick Lacolley1
1INSERM UMR_1116, Nancy, France
2CNRS UMR_S 8256, Paris, France
3BMCT FR3209 CNRS PTIBC IBISA, Nancy, France
Available Online 24 November 2016.
DOI
10.1016/j.artres.2016.10.023How to use a DOI?
Abstract

Integrin αv functions as a receptor for adhesion proteins and is expressed at high density in vascular smooth muscle cells (VSMC)1,2,3,4,5 whose phenotypic modulation plays a crucial role in arterial ageing and atherosclerosis.6,7.

Our aim was to define the arterial phenotype in mice conditionally inactivated for the integrin αv subunit in VSMC8,9,10(αv SMKO) and its role in angiotensin II (AngII)-induced arterial fibrosis. Transgenic mice αv SMKO and their control littermates (WT) were treated with two doses of AngII, low (0.3 mg/kg/day) and high (1.5 mg/kg/day), for 4 weeks.

At baseline, blood pressure was lower in αvSMKO compared to WT mice. Carotid distensibility was increased in αv SMKO mice (13.3±0.7 vs 10.3±0.6 mmHg−1.10−3). With low dose AngII isobaric distensibility remained higher in αvSMKOmice (12.4±1.2 vs 10.7±1.0 mmHg−1.10−3).With high dose AngII the increase in collagen content in carotid media was lower in αvSMKOthan in WT (19 vs 35%) for a similar increase in blood pressure (30 mmHg) and arterial wall hypertrophy. Collagen immunostaining and fluorescence measurements (multiphoton microscopy second harmonic generation) confirmed that high dose AngII induced lower increases in collagen content in αvSMKO mice versus WT (8.9±1.7 vs 14.2±1.4 greyscale mean/pixel). The combination of similar arterial wall hypertrophy with less fibrosis in mutant mice explains an increased distensibility in response to AngII.

The αv subunit regulates AngII-induced arterial fibrosis as determined by collagen staining, immunostaining and fluorescence. Pharmacological targeting of vascular αv integrin may have clinical applications in the treatment of patients with fibrosis associated with hypertension and atherosclerosis.

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This is an open access article distributed under the CC BY-NC license.

References

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Journal
Artery Research
Volume-Issue
16 - C
Pages
54 - 55
Publication Date
2016/11/24
ISSN (Online)
1876-4401
ISSN (Print)
1872-9312
DOI
10.1016/j.artres.2016.10.023How to use a DOI?
Open Access
This is an open access article distributed under the CC BY-NC license.

Cite this article

risenwbib
TY  - JOUR
AU  - Ekaterina Belozertseva
AU  - Huguette Louis
AU  - Zhenlin Li
AU  - Mustapha Bourhim
AU  - Dominique Dumas
AU  - Veronique Regnault
AU  - Patrick Lacolley
PY  - 2016
DA  - 2016/11/24
TI  - 4.4 ARTERIAL PHENOTYPE MODULATION AND REGULATION OF VASCULAR FIBROSIS IN MICE BY CONDITIONAL INACTIVATION OF INTEGRIN AV SUBUNIT IN VASCULAR SMOOTH MUSCLE CELLS
JO  - Artery Research
SP  - 54
EP  - 55
VL  - 16
IS  - C
SN  - 1876-4401
UR  - https://doi.org/10.1016/j.artres.2016.10.023
DO  - 10.1016/j.artres.2016.10.023
ID  - Belozertseva2016
ER  -