Hepatic Forkhead Box Protein A3 Regulates ApoA-I (Apolipoprotein A-I) Expression, Cholesterol Efflux, and Atherogenesis

Title

Hepatic Forkhead Box Protein A3 Regulates ApoA-I (Apolipoprotein A-I) Expression, Cholesterol Efflux, and Atherogenesis

Creator

Li Yuanyuan; Xu Yanyong; Jadhav Kavita; Zhu Yingdong; Yin Liya; Zhang Yanqiao

Publisher

Arteriosclerosis, Thrombosis, and Vascular Biology

Date

2019
2019-08

Description

OBJECTIVE: To determine the role of hepatic FOXA3 (forkhead box A3) in lipid metabolism and atherosclerosis. Approach and Results: Hepatic FOXA3 expression was reduced in diabetic or high fat diet-fed mice or patients with nonalcoholic steatohepatitis. We then used adenoviruses to overexpress or knock down hepatic FOXA3 expression. Overexpression of FOXA3 in the liver increased hepatic ApoA-I (apolipoprotein A-I) expression, plasma HDL-C (high-density lipoprotein cholesterol) level, macrophage cholesterol efflux, and macrophage reverse cholesterol transport. In contrast, knockdown of hepatic FOXA3 expression had opposite effects. We further showed that FOXA3 directly bound to the promoter of the Apoa1 gene to regulate its transcription. Finally, AAV8 (adeno-associated virus serotype 8)-mediated overexpression of human FOXA3 in the hepatocytes of Apoe-/- (apolipoprotein E-deficient) mice raised plasma HDL-C levels and significantly reduced atherosclerotic lesions. CONCLUSIONS: Hepatocyte FOXA3 protects against atherosclerosis by inducing ApoA-I and macrophage reverse cholesterol transport.

Subject

activation; Atherosclerosis; Cardiovascular System & Cardiology; cholesterol efflux; fatty-acids; FOXA3; FOXA3; gene; Hematology; high-density-lipoprotein; increased; Liver; Macrophages; mice lacking; nuclear factor 3-gamma; transport

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Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

1574-1587

Issue

8

Volume

39

Citation

Li Yuanyuan; Xu Yanyong; Jadhav Kavita; Zhu Yingdong; Yin Liya; Zhang Yanqiao, “Hepatic Forkhead Box Protein A3 Regulates ApoA-I (Apolipoprotein A-I) Expression, Cholesterol Efflux, and Atherogenesis,” NEOMED Bibliography Database, accessed January 23, 2021, https://neomed.omeka.net/items/show/6517.

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