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Arteriosclerosis, Thrombosis, Vascular Biology
Session Title: Lipid-mediated Mechanisms Contributing to Atherogenesis

Abstract 14120: The Natural Flavone Acacetinslows the Development of Atherosclerosis by Sirt3-Mediated Activation of AMPK Signaling Pathway in Diabetic ApoE Null Mice

Originally publishedCirculation. 2019;140:A14120

    Background: It is well recognized that the risk for atherosclerosis is remarkably increased in diabetes mellitus. The present study investigates whether the natural flavone acacetin can slow the development of atherosclerosis in diabetes mellitus of ApoE null mice.

    Methods: ApoE null mice with type-2 diabetes mellitus (DM) induced by streptozotocin were treated with acacetin (20 mg/kg, s.c., b,i,d.) for 12 weeks. Human umbilical vein endothelial cells (HUVECs) were cultured with high glucose (33 mM) medium with or without treatment of acacetin to explore the potential molecular mechanisms.

    Results: Atherosclerotic plaque area of aorta was significantly increased in DM mice to 10.99±1.02% from 5.07±0.32% of control (n=11, P<0.01) while reduced to 7.01±0.59 % (n=11, P<0.01) in DM mice treated with acacetin (see figure). Acacetin did not reduce random blood glucose level (21.30±1.10 mM vs. 23.07±1.35 mM in DM). Interestingly, it decreased the plasma TG, TC, LDL from 3.99±0.39 mM, 21.72±1.13 mM, 6.39±0.49 mM in vehicle-treated DM mice respectively to 2.69±0.19 mM, 16.28±0.94 mM, 4.39±0.53 mM in acacetin-treated animals. Moreover, acacetin increased plasma from HDL 0.48±0.03 mM to 0.64±0.02 mM (n=11, P<0.01). In cultured HUVECs, acacetin (0.3-3 uM) reversed the cell viability reduction, apoptosis, mitochondrial injury induced by high glucose culture via rescuing Nrf2, SOD1, SOD2, Bcl2/Bax reduction. These protective effects were associated with up-regulation of Sirt3 and LKB1-AMPK phosphorylation.

    Conclusions: Our results demonstrate for the first time that acacetin exerts an anti-atherosclerotic action in diabetic ApoE null mice via activating Sirt3- LKB1-AMPK signaling pathway, suggesting that acacetin may be an effective therapeutic drug for diabetic cardiovascular complications.

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