Next Article in Journal
Deciphering the Origin and Evolution of the X1X2Y System in Two Closely-Related Oplegnathus Species (Oplegnathidae and Centrarchiformes)
Next Article in Special Issue
Arterial Stiffness Assessed by Cardio-Ankle Vascular Index
Previous Article in Journal
Identification of Jasmonic Acid Biosynthetic Genes in Sweet Cherry and Expression Analysis in Four Ancient Varieties from Tuscany
Previous Article in Special Issue
Premature Vascular Aging in Guinea Pigs Affected by Fetal Growth Restriction
Open AccessArticle

High Mobility Group Box 1 Mediates TMAO-Induced Endothelial Dysfunction

Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204, USA
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(14), 3570; https://doi.org/10.3390/ijms20143570
Received: 7 June 2019 / Revised: 12 July 2019 / Accepted: 15 July 2019 / Published: 22 July 2019
(This article belongs to the Special Issue Endothelial Dysfunction: Pathophysiology and Molecular Mechanisms)
The intestinal microbe-derived metabolite trimethylamine N-oxide (TMAO) is implicated in the pathogenesis of cardiovascular diseases (CVDs). The molecular mechanisms of how TMAO induces atherosclerosis and CVDs’ progression are still unclear. In this regard, high-mobility group box protein 1 (HMGB1), an inflammatory mediator, has been reported to disrupt cell–cell junctions, resulting in vascular endothelial hyper permeability leading to endothelial dysfunction. The present study tested whether TMAO associated endothelial dysfunction results via HMGB1 activation. Biochemical and RT-PCR analysis showed that TMAO increased the HMGB1 expression in a dose-dependent manner in endothelial cells. However, prior treatment with glycyrrhizin, an HMGB1 binder, abolished the TMAO-induced HMGB1 production in endothelial cells. Furthermore, Western blot and immunofluorescent analysis showed significant decrease in the expression of cell–cell junction proteins ZO-2, Occludin, and VE-cadherin in TMAO treated endothelial cells compared with control cells. However, prior treatment with glycyrrhizin attenuated the TMAO-induced cell–cell junction proteins’ disruption. TMAO increased toll-like receptor 4 (TLR4) expression in endothelial cells. Inhibition of TLR4 expression by TLR4 siRNA protected the endothelial cells from TMAO associated tight junction protein disruption via HMGB1. In conclusion, our results demonstrate that HMGB1 is one of the important mediators of TMAO-induced endothelial dysfunction. View Full-Text
Keywords: HMGB1; TMAO; tight junction; ZO2; glycyrrhizin HMGB1; TMAO; tight junction; ZO2; glycyrrhizin
Show Figures

Figure 1

MDPI and ACS Style

Singh, G.B.; Zhang, Y.; Boini, K.M.; Koka, S. High Mobility Group Box 1 Mediates TMAO-Induced Endothelial Dysfunction. Int. J. Mol. Sci. 2019, 20, 3570.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop