Antioxidants | |
Myeloid GRK2 Regulates Obesity-Induced Endothelial Dysfunction by Modulating Inflammatory Responses in Perivascular Adipose Tissue | |
Marta Cruces-Sande1  AlbaC. Arcones1  Federico Mayor1  Cristina Murga1  AnaM. Briones2  Raquel Rodrigues-Díez2  Mercedes Salaices2  María González-Amor2  Rocío Vila-Bedmar3  Rosa Moreno-Carriles4  | |
[1] Ciber de Enfermedades Cardiovasculares (CIBERCV), 28028 Madrid, Spain;Departamento Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, Instituto de Investigación Hospital La Paz, 28029 Madrid, Spain;Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos (URJC), 28022 Madrid, Spain;Servicio de Angiología y Cirugía Vascular, Hospital Universitario La Princesa, 28006 Madrid, Spain; | |
关键词: perivascular adipose tissue (PVAT); G protein-coupled receptor kinase 2 (GRK2); tumor necrosis factor-α (TNFα); NADPH oxidase (Nox); endothelial dysfunction; | |
DOI : 10.3390/antiox9100953 | |
来源: DOAJ |
【 摘 要 】
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.
【 授权许可】
Unknown