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C1q/TNF-related protein-9 attenuates atherosclerosis through AMPK-NLRP3 inflammasome singling pathway.

Abstract：

BACKGROUNDS:C1q tumor necrosis factor-related protein 9 (CTRP9) has been suggested to exert an atheroprotective effect by modulating the inflammation, foam cell formation, endothelia and smooth muscle cell function via Adenosine Monophosphate Activated Protein Kinase (AMPK) pathway. On the other hand, the NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome plays an critical role in the atherosclerosis development, which is regulated by the AMPK. However, whether the CTRP9 affects the activity of NLRP3 inflammasome during the atherosclerosis development remains unclear, which would be elucidated in the current study. METHODS:The macrophage cells were stimulated with the oxidized low-density lipoprotein (ox-LDL) and also treated with the recombinant CTRP9 in the meantime. The activation of NLRP3 inflammasome was determined by measuring the releasing of IL-1β and caspase-1 p10 via ELISA and western blot, respectively. Then the AMPK was inhibited in macrophages by Dorsomorphin. Finally, the CTRP9-AMPK-NLRP3 inflammasome pathway was validated in the mouse model of atherosclerosis. RESULTS:The CTRP9 could down-regulate the expression of NLRP3 protein and also the activity of NLRP3 inflammasome in the ox-LDL activated macrophages. Inhibiting the AMPK significantly restored the activities of NLRP3 inflammasome. In the apolipoprotein E-deficient mice, lentiviral expression of CTRP9 could suppress the atherosclerosis development, which could be abolished by AMPK inhibition. CONCLUSION:Our data here indicated that the CTRP9 showed atheroprotective function via CTRP9-AMPK- NLRP3 inflammasome pathway.

journal_name

Int Immunopharmacol

journal_title

International immunopharmacology

authors

Zhang H,Gong X,Ni S,Wang Y,Zhu L,Ji N

doi

10.1016/j.intimp.2019.105934

subject

Has Abstract

pub_date

2019-12-01 00:00:00

pages

105934

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(19)31778-3

journal_volume

77

pub_type

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