Vascular Surgery Department, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Biochem Biophys Res Commun. 2020 Dec 17;533(4):1012-1020. doi: 10.1016/j.bbrc.2020.09.082. Epub 2020 Oct 2.
Macrophages contribute to abdominal aortic aneurysm (AAA), but the effect of macrophage on AAA formation is not totally understood. Recent research proved that macrophage pyroptosis plays an important role in many cardiovascular disease. However, whether macrophage pyroptosis is involved in AAA and its mechanism remains unknown. In this study, we found that the pyroptosis significantly increased in AAA tissues. β5i inhibitor PR-957 treatment or β5i deficiency markedly ameliorated AAA formation and decreased the pyroptosis. Pyroptosis were also significantly attenuated in bone marrow derived macrophages (BMDM) from β5i mice compared with the control group when they were subjected to OXLDL. Mechanistically, β5i may promote activation of NFκB which augment NLRP3 expression. In conclusion, this study suggested macrophages pyroptosis are involved in AAA and inhibition or knockout of β5i decreased macrophage pyroptosis via IκB/NFκB pathway.
巨噬细胞有助于腹主动脉瘤（AAA）的形成，但巨噬细胞对 AAA 形成的影响尚未完全阐明。最近的研究证实，巨噬细胞细胞焦亡在许多心血管疾病中发挥着重要作用。然而，巨噬细胞细胞焦亡是否参与 AAA 及其机制尚不清楚。在本研究中，我们发现 AAA 组织中的细胞焦亡明显增加。β5i 抑制剂 PR-957 治疗或β5i 缺乏可显著改善 AAA 的形成并减少细胞焦亡。与对照组相比，当β5i 敲除的骨髓来源巨噬细胞（BMDM）受到 OXLDL 刺激时，细胞焦亡也明显减弱。在机制上，β5i 可能促进 NFκB 的激活，从而增加 NLRP3 的表达。综上所述，本研究表明，巨噬细胞细胞焦亡参与了 AAA，抑制或敲除β5i 通过 IκB/NFκB 途径减少巨噬细胞细胞焦亡。
