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Endothelial G protein-coupled receptor kinase 2 regulates vascular homeostasis through the control of free radical oxygen species.


ABSTRACT: The role of endothelial G protein-coupled receptor kinase 2 (GRK2) was investigated in mice with selective deletion of the kinase in the endothelium (Tie2-CRE/GRK2(fl/fl)).Aortas from Tie2-CRE/GRK2(fl/fl) presented functional and structural alterations as compared with control GRK2(fl/fl) mice. In particular, vasoconstriction was blunted to different agonists, and collagen and elastic rearrangement and macrophage infiltration were observed. In primary cultured endothelial cells deficient for GRK2, mitochondrial reactive oxygen species was increased, leading to expression of cytokines. Chronic treatment with a reactive oxygen species scavenger in mice corrected the vascular phenotype by recovering vasoconstriction, structural abnormalities, and reducing macrophage infiltration.These results demonstrate that GRK2 removal compromises vascular phenotype and integrity by increasing endothelial reactive oxygen species production.

SUBMITTER: Ciccarelli M 

PROVIDER: S-EPMC4262246 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Endothelial G protein-coupled receptor kinase 2 regulates vascular homeostasis through the control of free radical oxygen species.

Ciccarelli Michele M   Sorriento Daniela D   Franco Antonietta A   Fusco Anna A   Del Giudice Carmine C   Annunziata Roberto R   Cipolletta Ersilia E   Monti Maria Gaia MG   Dorn Gerald W GW   Trimarco Bruno B   Iaccarino Guido G  

Arteriosclerosis, thrombosis, and vascular biology 20130815 10


<h4>Objective</h4>The role of endothelial G protein-coupled receptor kinase 2 (GRK2) was investigated in mice with selective deletion of the kinase in the endothelium (Tie2-CRE/GRK2(fl/fl)).<h4>Approach and results</h4>Aortas from Tie2-CRE/GRK2(fl/fl) presented functional and structural alterations as compared with control GRK2(fl/fl) mice. In particular, vasoconstriction was blunted to different agonists, and collagen and elastic rearrangement and macrophage infiltration were observed. In prima  ...[more]

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