Perivascular adipose tissue dysfunction aggravates adventitial remodeling in obese mini pigs via NLRP3 inflammasome/IL-1 signaling pathway

Acta Pharmacologica Sinica
Xiao ZhuKai Yin

Abstract

Perivascular adipose tissue (PVAT), a special type of adipose tissue, closely surrounds vascular adventitia and produces numerous bioactive substances to maintain vascular homeostasis. PVAT dysfunction has a crucial role in regulating vascular remodeling, but the exact mechanisms remain unclear. In this study, we investigated whether and how obesity-induced PVAT dysfunction affected adventitia remodeling in early vascular injury stages. Mini pigs were fed a high sugar and fat diet for 6 months to induce metabolic syndrome and obesity. In the mini pigs, left carotid vascular injury was then generated using balloon dilation. Compared with normal mini pigs, obese mini pigs displayed significantly enhanced vascular injury-induced adventitial responses, evidenced by adventitia fibroblast (AF) proliferation and differentiation, and adventitia fibrosis, as well as exacerbated PVAT dysfunction characterized by increased accumulation of resident macrophages, particularly the M1 pro-inflammatory phenotype, increased expression of leptin and decreased expression of adiponectin, and production of pro-inflammatory cytokines interleukin (IL)-1β and IL-18. Primary AFs cultured in PVAT-conditioned medium from obese mini pigs also showed signif...Continue Reading

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Citations

Mar 24, 2020·The Biochemical Journal·Nicole G BarraJonathan D Schertzer
May 12, 2020·Antioxidants & Redox Signaling·Hengjing HuLin Chang
Oct 2, 2020·Acta Pharmacologica Sinica·Zhu-Wei MiaoChao-Yu Miao
Jun 18, 2020·International Journal of Molecular Sciences·Kelvin Ka-Lok WuKenneth King-Yip Cheng
Sep 4, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Ha Won KimNeal L Weintraub
Dec 18, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Tong Wei (魏彤)Weili Shen (沈伟利)
Dec 24, 2019·The American Journal of Pathology·Maria G Tinajero, Avrum I Gotlieb
Mar 9, 2021·Frontiers in Nutrition·Alistaire D RuggieroKylie Kavanagh
Jan 14, 2022·Acta Pharmacologica Sinica·Chao YeXiu-Zhen Li

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Methods Mentioned

BETA
ELISA
light microscopy
protein assay
PCR
immunoprecipitation

Software Mentioned

Pro plus
Image
GraphPad Prism

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