Endothelial Nlrp3 inflammasome activation is associated with endothelial function in mice fed a methionine choline-deficient diet

OBJECTIVE Nonalcoholic fatty liver disease（NAFLD） is characterized by steatosis, liver inflammation and fibrosis, and increases the risk of endothelial dysfunction, but the molecular mechanisms between NAFLD and vascular endothelial dysfunction is still unclear. In this study, we explore whether Endothelial Nlrp3 inflammasome play a role in the process of endothelial dysfunction induced by NAFLD. METHODS Male C57 BL/6 J wildtype(Nlrp3;) mice were fed with either amethionine and choline deficient（MCD） diet or methionine and choline sufficient（MCS） diet for 2, 4 and 6 weeks, then determining NAFLD phenotype and vascular endothelial function.RESULTS Wild-typemice fed with MCD diet developed steatohepatitis and endothelial dysfunction. The expression of e NOS, ZO-1, ZO-2 and VE-cadherin in vascular endothelium was decreased at 2,4 and 6 weeks, meanwhile, ICAM-1, Nlrp3, Caspase-1 was increased. CONCLUSION NAFLD induced endothelial dysfunction and increases vascular permeability via NLRP3 activation.