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PRKAA1/AMPKα1-driven glycolysis in endothelial cells exposed to disturbed flow protects against atherosclerosis

Author

Listed:
  • Qiuhua Yang

    (Peking University Shenzhen Graduate School
    Augusta University)

  • Jiean Xu

    (Peking University Shenzhen Graduate School
    Augusta University)

  • Qian Ma

    (Peking University Shenzhen Graduate School
    Augusta University)

  • Zhiping Liu

    (Peking University Shenzhen Graduate School
    Augusta University)

  • Varadarajan Sudhahar

    (Augusta University)

  • Yapeng Cao

    (Peking University Shenzhen Graduate School
    Augusta University)

  • Lina Wang

    (Peking University Shenzhen Graduate School
    Augusta University)

  • Xianqiu Zeng

    (Peking University Shenzhen Graduate School
    Augusta University)

  • Yaqi Zhou

    (Peking University Shenzhen Graduate School
    Augusta University)

  • Min Zhang

    (Augusta University)

  • Yiming Xu

    (Augusta University
    Guangzhou Medical University)

  • Yong Wang

    (Augusta University
    Chengdu University of Traditional Chinese Medicine)

  • Neal L. Weintraub

    (Augusta University)

  • Chunxiang Zhang

    (University of Alabama at Birmingham)

  • Tohru Fukai

    (Augusta University)

  • Chaodong Wu

    (Texas A&M University)

  • Lei Huang

    (Peking University Shenzhen Hospital)

  • Zhen Han

    (Peking University Shenzhen Hospital)

  • Tao Wang

    (Peking University Shenzhen Hospital)

  • David J. Fulton

    (Augusta University)

  • Mei Hong

    (Peking University Shenzhen Graduate School)

  • Yuqing Huo

    (Augusta University)

Abstract

Increased aerobic glycolysis in endothelial cells of atheroprone areas of blood vessels has been hypothesized to drive increased inflammation and lesion burden but direct links remain to be established. Here we show that endothelial cells exposed to disturbed flow in vivo and in vitro exhibit increased levels of protein kinase AMP-activated (PRKA)/AMP-activated protein kinases (AMPKs). Selective deletion of endothelial Prkaa1, coding for protein kinase AMP-activated catalytic subunit alpha1, reduces glycolysis, compromises endothelial cell proliferation, and accelerates the formation of atherosclerotic lesions in hyperlipidemic mice. Rescue of the impaired glycolysis in Prkaa1-deficient endothelial cells through Slc2a1 overexpression enhances endothelial cell viability and integrity of the endothelial cell barrier, and reverses susceptibility to atherosclerosis. In human endothelial cells, PRKAA1 is upregulated by disturbed flow, and silencing PRKAA1 reduces glycolysis and endothelial viability. Collectively, these results suggest that increased glycolysis in the endothelium of atheroprone arteries is a protective mechanism.

Suggested Citation

  • Qiuhua Yang & Jiean Xu & Qian Ma & Zhiping Liu & Varadarajan Sudhahar & Yapeng Cao & Lina Wang & Xianqiu Zeng & Yaqi Zhou & Min Zhang & Yiming Xu & Yong Wang & Neal L. Weintraub & Chunxiang Zhang & To, 2018. "PRKAA1/AMPKα1-driven glycolysis in endothelial cells exposed to disturbed flow protects against atherosclerosis," Nature Communications, Nature, vol. 9(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07132-x
    DOI: 10.1038/s41467-018-07132-x
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    Cited by:

    1. Khairul Anwar Zarkasi & Nor Azian Abdul Murad & Norfazilah Ahmad & Rahman Jamal & Noraidatulakma Abdullah, 2022. "Coronary Heart Disease in Type 2 Diabetes Mellitus: Genetic Factors and Their Mechanisms, Gene-Gene, and Gene-Environment Interactions in the Asian Populations," IJERPH, MDPI, vol. 19(2), pages 1-44, January.

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