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

Authors:
Michele Ciccarelli
Michele Ciccarelli
University of Salerno
Fisciano | Italy
Daniela Sorriento
Daniela Sorriento
Department of Clinical Medicine
Italy
Antonietta Franco
Antonietta Franco
Washington University School of Medicine
Italy
Anna Fusco
Anna Fusco
Federico II University
Roberto Annunziata
Roberto Annunziata
Università Federico II
Italy
Ersilia Cipolletta
Ersilia Cipolletta
Department of Clinical Medicine
Italy
Maria Gaia Monti
Maria Gaia Monti
University Federico II
Italy

Arterioscler Thromb Vasc Biol 2013 Oct 15;33(10):2415-24. Epub 2013 Aug 15.

From the Department of Medicine and Surgery, University of Salerno, Salerno, Italy (M.C., E.C., G.l.); Department of Pharmacology, Center for Translational Medicine, Temple University, Philadelphia, PA (M.C.); Department of Biomedical Sciences, University of Naples Federico II, Naples, Italy (D.S., A.F., C.D.G., R.A., M.G.M., B.T.); Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO (G.W.D.); and IRCCS Multimedica, Milan, Italy (G.I.).

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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http://dx.doi.org/10.1161/ATVBAHA.113.302262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4262246PMC
October 2013
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11 Citations
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References

(Supplied by CrossRef)
A mutation of the beta 2-adrenergic receptor impairs agonist activation of adenylyl cyclase without affecting high affinity agonist binding. Distinct molecular determinants of the receptor are involved in physical coupling to and functional activation of Gs.
Hausdorff WP et al.
J Biol Chem 1990

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