School of Medicine, Qingdao University, Qingdao, China.
Department of Cardiology, Yuhuangding Hospital, The Fourth School of Clinical Medicine of Qingdao University, Yantai, Yantai, China.
FASEB J. 2023 May;37(5):e22933. doi: 10.1096/fj.202201762RR.
FURIN, a member of the mammalian proprotein convertases (PCs) family, can promote the proteolytic maturation of proproteins. It has been shown that FURIN plays an important role in the progression of atherosclerosis (AS). Current evidence indicates that autophagy widely participates in atherogenesis. This study aimed to explore whether FURIN could affect atherogenesis via autophagy. The effect of FURIN on autophagy was studied using aortic tissues from aortic dissection patients who had BENTALL surgery, as well as macrophages and ApoE-/- mice. In atherosclerotic plaques of aortic tissues from patients, FURIN expression and autophagy were elevated. In macrophages, FURIN-shRNA and FURIN-overexpression lentivirus were used to intervene in FURIN expression. The results showed that FURIN overexpression accelerated LC3 formation in macrophages during the autophagosome formation phase. Furthermore, FURIN-induced autophagy resulted in lower lipid droplet concentrations in macrophages. The western blot revealed that FURIN regulated autophagy via the AMPK/mTOR/ULK1/PI3KIII signaling pathway. In vivo, FURIN overexpression resulted in increased macrophage LC3 formation in ApoE-/- mice atherosclerotic plaques, confirming that FURIN could inhibit the progression of AS by promoting macrophage autophagy. The present study demonstrated that FURIN suppressed the progression of AS by promoting macrophage autophagy via the AMPK/mTOR/ULK1/PI3KIII signaling pathway, which attenuated atherosclerotic lesion formation. Based on this data, current findings add to our understanding of the complexity of AS.
脯氨酰羧肽酶（furin）是哺乳动物蛋白原转化酶（PCs）家族的一员，可促进蛋白原的蛋白水解成熟。已有研究表明，furin 在动脉粥样硬化（AS）的进展中发挥着重要作用。目前的证据表明，自噬广泛参与动脉粥样硬化的形成。本研究旨在探讨 furin 是否可以通过自噬影响动脉粥样硬化的形成。本研究使用接受 Bentall 手术的主动脉夹层患者的主动脉组织、巨噬细胞和 ApoE-/- 小鼠来研究 furin 对自噬的影响。在患者主动脉组织的粥样硬化斑块中，furin 表达和自噬均升高。在巨噬细胞中，使用 furin-shRNA 和 furin 过表达慢病毒干预 furin 表达。结果表明，furin 过表达加速了自噬体形成阶段巨噬细胞中的 LC3 形成。此外，furin 诱导的自噬导致巨噬细胞中脂质滴浓度降低。Western blot 显示 furin 通过 AMPK/mTOR/ULK1/PI3KIII 信号通路调节自噬。在体内，Furin 过表达导致 ApoE-/- 小鼠动脉粥样硬化斑块中巨噬细胞 LC3 形成增加，证实 furin 可以通过促进巨噬细胞自噬来抑制 AS 的进展。本研究表明，furin 通过 AMPK/mTOR/ULK1/PI3KIII 信号通路促进巨噬细胞自噬来抑制 AS 的进展，从而减轻动脉粥样硬化病变的形成。基于这些数据，目前的研究结果增加了我们对 AS 复杂性的理解。
