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

Michele Ciccarelli, Daniela Sorriento, Antonietta Franco, Anna Fusco, Carmine Del Giudice, Roberto Annunziata, Ersilia Cipolletta, Maria Gaia Monti, Gerald W. Dorn, Bruno Trimarco, Guido Iaccarino

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

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). APPROACH AND RESULTS - : Aortas from Tie2-CRE/GRK2 presented functional and structural alterations as compared with control GRK2 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.

Original languageEnglish
Pages (from-to)2415-2424
Number of pages10
JournalArteriosclerosis, thrombosis, and vascular biology
Volume33
Issue number10
DOIs
StatePublished - Oct 2013

Keywords

  • G protein-coupled receptor kinases
  • endothelial cells
  • mitochondria
  • vascular medicine

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