Myeloid GRK2 regulates obesity-induced endothelial dysfunction by modulating inflammatory responses in perivascular adipose tissue
Entity
UAM. Departamento de Biología Molecular; UAM. Departamento de FarmacologíaPublisher
MDPIDate
2020-10-04Citation
10.3390/antiox9100953
Antioxidants 9.10 (2020): 953
ISSN
2076-3921DOI
10.3390/antiox9100953Project
Gobierno de España. SAF2017-84125-R; Gobierno de España. SAF 2016-80305-P; Comunidad de Madrid. S2017/BMD-3671/INFLAMUNE-CM; Comunidad de Madrid. B2017/BMD-3676/AORTASANAEditor's Version
https://doi.org/10.3390/antiox9100953Subjects
Fat Thickness; Adipose Tissues; Coronary Artery Disease; Biología y Biomedicina / BiologíaRights
© 2020 by the authorsAbstract
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
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Google Scholar:González-Amor, María
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Vila-Bedmar, Rocío
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Rodrigues Díez, Raquel
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Moreno-Carriles, Rosa
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Concepción Arcones, Alba
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Cruces-Sande, Marta
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Salaices, Mercedes
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Mayor Menéndez, Federico
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Briones, Ana M.
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Murga Montesinos, Cristina
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