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


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.
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.).
Michele
M
Ciccarelli
Daniela
D
Sorriento
Antonietta
A
Franco
Anna
A
Fusco
Carmine
C
Del Giudice
Roberto
R
Annunziata
Ersilia
E
Cipolletta
Maria Gaia
MG
Monti
Gerald W
GW
Dorn
Bruno
B
Trimarco
Guido
G
Iaccarino
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004547:Elastic Tissue / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000201:enzymology* / Q000473:pathology; D016166:Free Radical Scavengers / Q000494:pharmacology; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006706:Homeostasis; D018836:Inflammation Mediators / Q000378:metabolism; D019426:Integrases / Q000235:genetics; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism*; D042787:Receptor, TIE-2 / Q000235:genetics; D015398:Signal Transduction; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D016207:Cytokines; D016166:Free Radical Scavengers; D018836:Inflammation Mediators; D017382:Reactive Oxygen Species; D014662:Vasoconstrictor Agents; D003094:Collagen; D042787:Receptor, TIE-2; C079086:Tek protein, mouse; C496568:GRK2 protein, mouse; D054769:G-Protein-Coupled Receptor Kinase 2; C045073:Cre recombinase; D019426:Integrases
G protein-coupled receptor kinases; endothelial cells; mitochondria; vascular medicine