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

Qiuhua Yang, Jiean Xu, Qian Ma, Zhiping Liu, Sudhahar Varadarajan, Yapeng Cao, Lina Wang, Xianqiu Zeng, Yaqi Zhou, Min Zhang, Yiming Xu, Yong Wang, Neal Lee Weintraub, Chunxiang Zhang, Tohru Fukai, Chaodong Wu, Lei Huang, Zhen Han, Tao Wang, David J FultonMei Hong, Yuqing Huo

Research output: Contribution to journalArticle

10 Scopus citations

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.

Original languageEnglish (US)
Article number4667
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Yang, Q., Xu, J., Ma, Q., Liu, Z., Varadarajan, S., Cao, Y., Wang, L., Zeng, X., Zhou, Y., Zhang, M., Xu, Y., Wang, Y., Weintraub, N. L., Zhang, C., Fukai, T., Wu, C., Huang, L., Han, Z., Wang, T., ... Huo, Y. (2018). PRKAA1/AMPKα1-driven glycolysis in endothelial cells exposed to disturbed flow protects against atherosclerosis. Nature communications, 9(1), [4667]. https://doi.org/10.1038/s41467-018-07132-x