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

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, Tohru Fukai, Chaodong Wu, Lei Huang, Zhen Han, Tao Wang, David J. Fulton, Mei Hong () and Yuqing Huo ()
Additional contact information
Qiuhua Yang: Peking University Shenzhen Graduate School
Jiean Xu: Peking University Shenzhen Graduate School
Qian Ma: Peking University Shenzhen Graduate School
Zhiping Liu: Peking University Shenzhen Graduate School
Varadarajan Sudhahar: Augusta University
Yapeng Cao: Peking University Shenzhen Graduate School
Lina Wang: Peking University Shenzhen Graduate School
Xianqiu Zeng: Peking University Shenzhen Graduate School
Yaqi Zhou: Peking University Shenzhen Graduate School
Min Zhang: Augusta University
Yiming Xu: Augusta University
Yong Wang: Augusta University
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

Nature Communications, 2018, vol. 9, issue 1, 1-17

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-07132-x

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