School of Medicine, Qingdao University, Qingdao, China.
Department of Cardiology, Yuhuangding Hospital, The Fourth School of Clinical Medicine of Qingdao University, Yantai, Shandong Province, China.
J Cardiovasc Transl Res. 2023 Oct;16(5):999-1009. doi: 10.1007/s12265-023-10390-w. Epub 2023 May 1.
It has been shown that SGLT2 suppresses atherosclerosis (AS). Recent studies indicate that autophagy widely participates in atherogenesis. This study aimed to assess the effect of canagliflozin (CAN) on atherogenesis via autophagy. Macrophages and ApoE - / - mice were used in this study. In macrophages, the results showed that CAN promoted LC3II expression and autophagosome formation. Furthermore, the cholesterol efflux assay demonstrated that CAN enhanced cholesterol efflux from macrophages via autophagy, resulting in lower lipid droplet concentrations in macrophages. The western blot revealed that CAN regulated autophagy via the AMPK/ULK1/Beclin1 signaling pathway. CAN resulted in increased macrophage autophagy in atherosclerotic plaques of ApoE - / - mice, confirming that CAN could inhibit the progression of AS via promoting macrophage autophagy. The current study found that CAN reduced the production of atherosclerotic lesions, which adds to our understanding of how SGLT2 inhibitors function to delay the progression of AS.
已有研究表明 SGLT2 可抑制动脉粥样硬化（AS）。近期研究表明自噬广泛参与动脉粥样硬化的形成。本研究旨在评估坎格列净（CAN）通过自噬对动脉粥样硬化形成的影响。本研究使用巨噬细胞和 ApoE-/-小鼠。在巨噬细胞中，结果表明 CAN 可促进 LC3II 的表达和自噬体的形成。此外，胆固醇外排实验表明，CAN 通过自噬促进巨噬细胞胆固醇外排，使巨噬细胞内的脂质滴浓度降低。Western blot 显示，CAN 通过 AMPK/ULK1/Beclin1 信号通路调节自噬。CAN 导致 ApoE-/-小鼠动脉粥样硬化斑块中的巨噬细胞自噬增加，证实 CAN 可通过促进巨噬细胞自噬抑制 AS 的进展。本研究发现 CAN 可减少动脉粥样硬化病变的产生，这有助于我们了解 SGLT2 抑制剂如何发挥作用以延缓 AS 的进展。
