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

First Author  Ciccarelli M Year  2013
Journal  Arterioscler Thromb Vasc Biol Volume  33
Issue  10 Pages  2415-24
PubMed ID  23950144 Mgi Jnum  J:222223
Mgi Id  MGI:5644140 Doi  10.1161/ATVBAHA.113.302262
Citation  Ciccarelli M, et al. (2013) Endothelial G protein-coupled receptor kinase 2 regulates vascular homeostasis through the control of free radical oxygen species. Arterioscler Thromb Vasc Biol 33(10):2415-24
abstractText  OBJECTIVE: 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)). APPROACH AND RESULTS: 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. CONCLUSIONS: These results demonstrate that GRK2 removal compromises vascular phenotype and integrity by increasing endothelial reactive oxygen species production.
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