Aortic dysfunction in metabolic syndrome mediated by perivascular adipose tissue TNFα‐ and NOX2‐dependent pathway

• Published in: Experimental physiology 2018-04, Vol.103 (4), p.590-603
• Main Authors: DeVallance, Evan, Branyan, Kayla W., Lemaster, Kent, Olfert, I. Mark, Smith, David M., Pistilli, Emidio E., Frisbee, Jefferson C., Chantler, Paul D.
• Format: Article
• Language: English
• Subjects: Adipose tissue; Adipose Tissue - metabolism; Adipose Tissue - physiopathology; Animals; Aorta; Aorta - metabolism; Aorta - physiopathology; Coronary vessels; CYBB protein; Endothelium; Endothelium, Vascular - metabolism; Endothelium, Vascular - physiopathology; Gelatinase B; Male; Matrix Metalloproteinase 9 - metabolism; Mechanical properties; Metabolic syndrome; Metabolic Syndrome - metabolism; Metabolic Syndrome - physiopathology; NAD(P)H oxidase; NADPH Oxidase 2 - metabolism; Nitric oxide; Nitric Oxide - metabolism; perivascular adipose tissue; Proteasome Endopeptidase Complex - metabolism; Proteasomes; Rats; Rats, Zucker; Reactive oxygen species; Reactive Oxygen Species - metabolism; Rodents; Signal Transduction - physiology; Structure-function relationships; Superoxide dismutase; Thorax; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; Tumors; tumour necrosis factor‐α; Vasoactive agents
• ISSN: 0958-0670; 1469-445X
• DOI: 10.1113/EP086818

New Findings What is the central question of this study? Tumour necrosis factor‐α (TNFα) has been shown to impair vascular function, but the impact of thoracic aorta perivascular adipose tissue (tPVAT)‐derived TNFα on tPVAT and aortic function in metabolic syndrome is unknown. What is the main finding and its importance? Release of TNFα by tPVAT causes production of reactive oxygen species in tPVAT through activation of an NADPH‐oxidase 2 (NOX2)‐dependent pathway, activates production of aortic reactive oxygen species and mediates aortic stiffness, potentially through matrix metalloproteinase 9 activity. Neutralization of TNFα and/or inhibition of NOX2 blocks the tPVAT‐induced impairment of aortic function. These data partly implicate tPVAT NOX2 and TNFα in mediating the vascular pathology of metabolic syndrome. Perivascular adipose tissue (PVAT) is recognized for its vasoactive effects, but it is unclear how metabolic syndrome impacts thoracic aorta (t)PVAT and the subsequent effect on functional and structural aortic stiffness. Thoracic aorta and tPVAT were removed from 16‐ to 17‐week‐old lean (LZR, n = 16) and obese Zucker rats (OZR, n = 16). The OZR presented with aortic endothelial dysfunction, assessed by wire myography, and increased aortic stiffness, assessed by elastic modulus. The OZR tPVAT exudate further exacerbated the endothelial dysfunction, reducing nitric oxide and endothelium‐dependent relaxation (P