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, ,

  • 1 Department of Cardiology, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
  • 2 Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
  • 3 Department of Cardiology, Affiliated Dingli Institute and Wenzhou Central Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
* Equal contribution

Received: May 9, 2020       Accepted: November 15, 2020       Published: January 20, 2021
How to Cite

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.


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.


Ang II: Angiotensin II; α-SMA: α-smooth muscle actin; CMC-Na: sodium carboxyl methyl cellulose; COL3: collagen type III; DMSO: dimethyl sulfoxide; ECs: endothelial cells; EGFP: enhanced green fluorescent protein; ERK: extracellular regulated protein kinases; IL-6: interleukin-6; JNK: c-Jun N-terminal kinase; MAPKs: mitogen-activated protein kinases; MDA: malondialdehyde; MD2: myeloid differentiation; NF-κB: nuclear facto r-kappa B; NOX4: NADPH-oxidase 4; PCNA: proliferating cell nuclear antigen; ROS: reactive oxygen species; ERK: extracellular regulated protein kinases; JNK: c-Jun N-terminal kinase; SIRT1: sirtuin1; SOD: superoxide dismutase; TNF-α: tumor necrosis factor-α; VSMCs: vascular smooth muscle cells.