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Myeloid GRK2 Regulates Obesity-Induced Endothelial Dysfunction by Modulating Inflammatory Responses in Perivascular Adipose Tissue

Authors :
María González-Amor
Rocío Vila-Bedmar
Raquel Rodrigues-Díez
Rosa Moreno-Carriles
Alba C. Arcones
Marta Cruces-Sande
Mercedes Salaices
Federico Mayor
Ana M. Briones
Cristina Murga
Source :
Antioxidants, Vol 9, Iss 10, p 953 (2020)
Publication Year :
2020
Publisher :
MDPI AG, 2020.

Abstract

Perivascular adipose tissue (PVAT) is increasingly being regarded as an important endocrine organ that directly impacts vessel function, structure, and contractility in obesity-associated diseases. We uncover here a role for myeloid G protein-coupled receptor kinase 2 (GRK2) in the modulation of PVAT-dependent vasodilation responses. GRK2 expression positively correlates with myeloid- (CD68) and lymphoid-specific (CD3, CD4, and CD8) markers and with leptin in PVAT from patients with abdominal aortic aneurysms. Using mice hemizygous for GRK2 in the myeloid lineage (LysM-GRK2+/−), we found that GRK2 deficiency in myeloid cells allows animals to preserve the endothelium-dependent acetylcholine or insulin-induced relaxation, which is otherwise impaired by PVAT, in arteries of animals fed a high fat diet (HFD). Downregulation of GRK2 in myeloid cells attenuates HFD-dependent infiltration of macrophages and T lymphocytes in PVAT, as well as the induction of tumor necrosis factor-α (TNFα) and NADPH oxidase (Nox)1 expression, whereas blocking TNFα or Nox pathways by pharmacological means can rescue the impaired vasodilator responses to insulin in arteries with PVAT from HFD-fed animals. Our results suggest that myeloid GRK2 could be a potential therapeutic target in the development of endothelial dysfunction induced by PVAT in the context of obesity.

Details

Language :
English
ISSN :
20763921
Volume :
9
Issue :
10
Database :
Directory of Open Access Journals
Journal :
Antioxidants
Publication Type :
Academic Journal
Accession number :
edsdoj.21fd34ceac941868de933bdea8cd246
Document Type :
article
Full Text :
https://doi.org/10.3390/antiox9100953