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 domain-like 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.

中文翻译：

---

脂联素上调miR-133a抑制焦磷酸化途径并挽救急性主动脉夹层。

急性主动脉夹层（AAD）是由在主动脉壁中层形成血肿引起的心血管急症。脂联素（APN）是具有抗发炎和抗动脉粥样硬化功能的脂肪组织特异性蛋白。作为炎症性细胞死亡的细胞凋亡取决于caspase1的激活，而核苷酸结合寡聚化域样受体蛋白3（NLRP3）是细胞凋亡途径的典型代表。在这项研究中，我们旨在确定APN是否会影响AAD流程。结果表明，APN过表达（OE）抑制了小鼠模型中AAD的发育以及葡萄糖，甘油三酸酯和总胆固醇的水平。此外，APN OE抑制了胃泌素D（GSDMD），NLRP3，caspase1，白介素-1β（IL-1β），IL-18和骨桥蛋白（OPN）的产生，体外和体内。此外，发现NLRP3是miR-133a的靶基因，miR-133a OE在减缓LPS诱导的GSDMD，NLRP3，caspase1，IL-1β，IL-18和OPN产生时，与APN OE具有相似的作用。以及血管平滑肌细胞（vSMC）中的α-SMA下调。此外，vSMC中的miR-133a敲除消除了APN OE的有益作用。总之，我们目前的结果表明，APN对miR-133a的上调抑制了焦磷酸化途径，从而可能挽救了AAD。