The SGLT2 Inhibitor Empagliflozin Attenuates Atherosclerosis Progression by Inducing Autophagy
Abstract
Abstract Background: Cardiovascular disease due to atherosclerosis（AS）is one of the leading causes of death worldwide. Sodium-dependent glucose transporters 2 inhibitor (SGLT2i ) (SGLT2i), empagliflozin(EMPA), is a new type of hypoglycemic drug .Recent studies have shown that EMPA not only reduces increased glucose, but also has cardiovascular protective effects and that it slows the process of AS.However, the underlying mechanism has yet to be defined.Methods: Male apoE -/- mice were fed a western high-fat diet to establish an AS model. The area and size of atherosclerotic lesions in apoE -/- mice were then assessed by hematoxylin–eosin (HE) staining after EMPA treatment . After EMPA treatment of the RAW 246.7 macrophage cell line, human aortic smooth muscle cells (HASMCs) and human umbilical vein endothelial cells (HUVECs),western blotting was applied to measure the levels of autophagy-related proteins and proinflammatory cytokines,GFP-LC3 puncta were detected by confocal microscopy to confirme autophagosome formation. Oil red staining was performed to detect the foaming of macrophages and HASMCs, flow cytometry was used for cell cycle analysis. EdU, CCK-8 and scratch assays were also performed to examine the cell proliferation and migration of HASMCs. Results: EMPA suppressed the progression of atherosclerotic lesions in apoE -/- mice. EMPA also induced autophagy in RAW 246.7 cells, HASMCs and HUVECs, and it significantly increased the expression of Beclin1 and the…
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