Upregulation of miR-133a by adiponectin inhibits pyroptosis pathway and rescues acute aortic dissection

摘要

Acute aortic dissection (AAD) is a cardiovascular emergency caused by the formation of hematoma in the middle layer of the aortic wall.Adiponectin (APN) is an adipose tissue-specific protein that has anti-inflammation and anti-atherosclerosis functions.Pyroptosis,as an inflammatory cell death,depends on the activation of caspase1,while nucleotide-binding oligomerization domainlike receptor protein 3 (NLRP3) is a typical representative of the pyroptosis pathway.In this study,we aimed to find whether APN affects the AAD process.The results showed that APN overexpression (OE) inhibited the AAD development and the levels of glucose,triglyceride,and total cholesterol in mice model.In addition,APN OE inhibited the productions of gasdermin D (GSDMD),NLRP3,caspase1,interleukin-1β (IL-1β),IL-18,and osteopontin (OPN),as well as α-smooth muscle actin (α-SMA) downregulation in vitro and in vivo.In addition,NLRP3 was found to be a target gene of miR-133a and miR-133a OE showed similar effects to APN OE in attenuating the LPS-induced productions of GSDMD,NLRP3,caspase1,IL-1β,IL-18,and OPN,as well as α-SMA downregulation in vascular smooth muscle cells (vSMCs).Moreover,the beneficial effects of APN OE were abolished by miR-133a knockdown in vSMCs.In conclusion,our present results indicated that the upregulation of miR-133a by APN inhibits pyroptosis pathway,which potentially rescues AAD.