P1.15 CONDITIONAL INACTIVATION OF INTEGRIN AV SUBUNIT IN VASCULAR SMOOTH MUSCLE CELLS REGULATES FIBROSIS IN VESSELS
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Integrin avb3 is expressed at high density in vascular smooth muscle cells (VSMCs). It functions as a receptor for adhesion proteins in VSMCs which phenotypic modulation plays a pivotal role in arteriosclerosis and atherosclerosis.
The aim was to study the role of integrin avb3 in angiotensin II (Ang II)-induced arterial fibrosis in mice and in human samples of atherosclerotic arteries in situ. Transgenic mice conditionally inactivated for integrin av subunit in VSMCs (avSMKO) were treated with Ang II (1,5 mg/kg/day) for 4 weeks. Immunostained slices of atherosclerotic plaques at different stages of development and primary cultures of human aortic VSMCs were used.
At baseline, blood pressure was lower in avSMKO compared to control (WT) mice. Isobaric carotid distensibility was increased and remained higher in avSMKO in response to Ang II. The increase in collagen content in response to Ang II was lower in avSMKO than in WT (15 vs 36%) for similar increase in blood pressure (20 mmHg) and arterial wall hypertrophy.
The immunohistochemistry of aortic slices showed stronger staining for integrin avb3 in atherosclerotic plaques compared to healthy aortas. In VSMC cultures, the mRNA of av was decreased.
In conclusion, these results show that avb3 is strongly expressed in neointimal proliferation and in fibrous plaques. The av integrin subunit seems to regulate arterial fibrosis in response to hypertension and plaque growth. Low RNA quantities of av subunit of VSMCs contrasted with strong protein staining in plaques suggesting the participation of inflammatory cells in the synthesis of this integrin.
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TY - JOUR AU - Ekaterina Belozertseva* AU - Melusine Didelot AU - Amel Mohamadi AU - Zhenlin Li AU - Huguette Louis AU - Jean-Baptiste Michel AU - Véronique Regnault AU - Patrick Lacolley PY - 2015 DA - 2015/11 TI - P1.15 CONDITIONAL INACTIVATION OF INTEGRIN AV SUBUNIT IN VASCULAR SMOOTH MUSCLE CELLS REGULATES FIBROSIS IN VESSELS JO - Artery Research SP - 6 EP - 6 VL - 12 IS - C SN - 1876-4401 UR - https://doi.org/10.1016/j.artres.2015.10.207 DO - https://doi.org/10.1016/j.artres.2015.10.207 ID - Belozertseva*2015 ER -