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Research Paper|Volume 13, Issue 3|pp 4409—4427

Myeloid differentiation 2 deficiency attenuates AngII-induced arterial vascular oxidative stress, inflammation, and remodeling

Shushi Huang1,2, Shengban You1, Jinfu Qian1,2, Chengyi Dai1,2, Siyuan Shen2, Jun Wang3, Weijian Huang1, Guang Liang1,2,3, Gaojun Wu1
  • 1Department of Cardiology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
  • 2Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
  • 3Department of Cardiology, Affiliated Dingli Institute and Wenzhou Central Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
* Equal contribution
Received: May 9, 2020Accepted: November 15, 2020Published: January 20, 2021
https://doi.org/10.18632/aging.202402

Copyright: © 2021 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Vascular remodeling is a pertinent target for cardiovascular therapy. Vascular smooth muscle cell (VSMC) dysfunction plays a key role in vascular remodeling. Myeloid differentiation 2 (MD2), a cofactor of toll-like receptor 4 (TLR4), is involved in atherosclerotic progress and cardiac remodeling via activation of chronic inflammation. In this study, we explored the role of MD2 in vascular remodeling using an Ang II-induced mouse model and cultured human aortic VSMCs. MD2 deficiency suppressed Ang II-induced vascular fibrosis and phenotypic switching of VSMCs without affecting blood pressure in mice. Mechanistically, MD2 deficiency prevented Ang II-induced expression of inflammatory cytokines and oxidative stress in mice and cultured VSMCs. Furthermore, MD2 deficiency reversed Ang II-activated MAPK signaling and Ang II-downregulated SIRT1 expression. Taken together, MD2 plays a significant role in Ang II-induced vascular oxidative stress, inflammation, and remodeling, indicating that MD2 is a potential therapeutic target for the treatment of vascular remodeling-related cardiovascular diseases.