Regulation of endothelial intracellular adenosine via adenosine kinase epigenetically modulates vascular inflammation

Yiming Xu, Yong Wang, Siyuan Yan, Qiuhua Yang, Yaqi Zhou, Xianqiu Zeng, Zhiping Liu, Xiaofei An, Haroldo Alfredo Flores Toque, Zheng Dong, Xuejun Jiang, David J Fulton, Neal Lee Weintraub, Qinkai Li, Zsolt Bagi, Mei Hong, Detlev Boison, Chaodong Wu, Yuqing Huo

Research output: Contribution to journalArticle

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Abstract

The molecular mechanisms underlying vascular inflammation and associated inflammatory vascular diseases are not well defined. Here we show that endothelial intracellular adenosine and its key regulator adenosine kinase (ADK) play important roles in vascular inflammation. Pro-inflammatory stimuli lead to endothelial inflammation by increasing endothelial ADK expression, reducing the level of intracellular adenosine in endothelial cells, and activating the transmethylation pathway through increasing the association of ADK with S-adenosylhomocysteine (SAH) hydrolase (SAHH). Increasing intracellular adenosine by genetic ADK knockdown or exogenous adenosine reduces activation of the transmethylation pathway and attenuates the endothelial inflammatory response. In addition, loss of endothelial ADK in mice leads to reduced atherosclerosis and affords protection against ischemia/reperfusion injury of the cerebral cortex. Taken together, these results demonstrate that intracellular adenosine, which is controlled by the key molecular regulator ADK, influences endothelial inflammation and vascular inflammatory diseases.

Original languageEnglish (US)
Article number986
JournalNature Communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

Fingerprint

Adenosine Kinase
adenosines
Adenosine
Blood Vessels
Inflammation
Vascular Diseases
Adenosylhomocysteinase
regulators
Endothelial cells
Reperfusion Injury
Cerebral Cortex
Atherosclerosis
Endothelial Cells
cerebral cortex
Chemical activation
Association reactions
arteriosclerosis
ischemia
stimuli
mice

ASJC Scopus subject areas

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

Cite this

Regulation of endothelial intracellular adenosine via adenosine kinase epigenetically modulates vascular inflammation. / Xu, Yiming; Wang, Yong; Yan, Siyuan; Yang, Qiuhua; Zhou, Yaqi; Zeng, Xianqiu; Liu, Zhiping; An, Xiaofei; Flores Toque, Haroldo Alfredo; Dong, Zheng; Jiang, Xuejun; Fulton, David J; Weintraub, Neal Lee; Li, Qinkai; Bagi, Zsolt; Hong, Mei; Boison, Detlev; Wu, Chaodong; Huo, Yuqing.

In: Nature Communications, Vol. 8, No. 1, 986, 01.12.2017.

Research output: Contribution to journalArticle

Xu, Yiming ; Wang, Yong ; Yan, Siyuan ; Yang, Qiuhua ; Zhou, Yaqi ; Zeng, Xianqiu ; Liu, Zhiping ; An, Xiaofei ; Flores Toque, Haroldo Alfredo ; Dong, Zheng ; Jiang, Xuejun ; Fulton, David J ; Weintraub, Neal Lee ; Li, Qinkai ; Bagi, Zsolt ; Hong, Mei ; Boison, Detlev ; Wu, Chaodong ; Huo, Yuqing. / Regulation of endothelial intracellular adenosine via adenosine kinase epigenetically modulates vascular inflammation. In: Nature Communications. 2017 ; Vol. 8, No. 1.
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