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Biochem Biophys Res Commun. 2016 Dec 2;481(1-2):63-70. doi: 10.1016/j.bbrc.2016.11.017. Epub 2016 Nov 8.

Trimethylamine N-oxide induces inflammation and endothelial dysfunction in human umbilical vein endothelial cells via activating ROS-TXNIP-NLRP3 inflammasome.

Author information

1
Department of Vascular and Thyroid Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, PR China; State Key Laboratory of Quality Research in Chinese Medicine (Macau University of Science and Technology), Avenida Wai Long, Taipa, Macau, PR China.
2
Department of Vascular Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, PR China.
3
Department of Vascular and Thyroid Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, PR China.
4
Department of Vascular and Thyroid Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, PR China. Electronic address: yzhe1573@163.com.
5
Department of Vascular Surgery, Qingdao Municipal Hospital, Qingdao, Shandong, 266000, PR China. Electronic address: yunhuichen520@163.com.

Abstract

Recent research demonstrates that the choline-derived metabolite trimethylamine-N-oxide (TMAO) levels are strongly associated with atherosclerosis and cardiovascular risks. The NLRP3 inflammasome responds to exogenous and endogenous danger signals involved in the development of atherosclerosis. Moreover, thioredoxin-interactive protein (TXNIP) activation is a key event linked to NLRP3 inflammasome via reactive oxygen species (ROS). Whether TMAO prime NLRP3 inflammasome via ROS-TXNIP pathway remains unclear. This study observed the expression of TXNIP-NLRP3 inflammasome stimulated by TMAO in human umbilical vein endothelial cells (HUVECs), aiming to elucidate the mechanism by which the TMAO may contribute to inflammation and endothelial dysfunction. Our data showed that TMAO significantly triggered oxidative stress and activated TXNIP-NLRP3 inflammasome whereat inflammatory cytokines interleukin (IL)-1β and IL-18 were released in a dose- and time-dependent manner, but endothelial nitric oxide synthase (eNOS) and production of nitric oxide (NO) were inhibited. Moreover, TMAO-mediated effects were observably reversed by ROS inhibitor N-acetylcysteine (NAC) treatment or siRNA-mediated knockdown TXPIN and NLRP3. Taken together, our results firstly reveal that TMAO induces inflammation and endothelial dysfunction via activating ROS-TXNIP-NLRP3 inflammasome, suggest a likely mechanism for TMAO-dependent enhancement in atherosclerosis and cardiovascular risks.

KEYWORDS:

Atherosclerosis; Endothelial dysfunction; NLRP3 inflammasome; Oxidative stress; Trimethylamine N-oxide

PMID:
27833015
DOI:
10.1016/j.bbrc.2016.11.017
[Indexed for MEDLINE]

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