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

DOI

10.1016/j.artres.2016.10.023How to use a DOI?

Abstract

Integrin α_v 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 α_v subunit in VSMC^8,9,10(α_v ^SMKO) and its role in angiotensin II (AngII)-induced arterial fibrosis. Transgenic mice α_v ^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 α_v^SMKO compared to WT mice. Carotid distensibility was increased in α_v ^SMKO mice (13.3±0.7 vs 10.3±0.6 mmHg^−1.10⁻³). With low dose AngII isobaric distensibility remained higher in α_v^SMKOmice (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 α_v^SMKOthan 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 α_v^SMKO 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 α_v subunit regulates AngII-induced arterial fibrosis as determined by collagen staining, immunostaining and fluorescence. Pharmacological targeting of vascular α_v integrin may have clinical applications in the treatment of patients with fibrosis associated with hypertension and atherosclerosis.

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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  -