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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 metabolicsyndrome 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 significantly increased proliferation and differentiation.We further revealed that activated nod-like receptor protein 3 (NLRP3) inflammasome and its downstream products,i.e.,IL-1 family members such as IL-1β and IL-18 were upregulated in the PVAT of obese mini pigs;PVAT dysfunction was also demonstrated in preadipocytes treated with palmitic acid.Finally,we showed that pretreatment with IL-1 receptor (IL-1R)antagonist or IL-1R knockdown blocked AF proliferation and differentiation in AFs cultured in PVAT-conditioned medium.These results demonstrate that obesity-induced PVAT dysfunction aggravates adventitial remodeling after early vascular injury with elevated AF proliferation and differentiation via activating the NLRP3/IL-1 signaling pathway.