Please use this identifier to cite or link to this item: http://cmuir.cmu.ac.th/jspui/handle/6653943832/71827
Title: Myeloid differentiation protein 2 mediates angiotensin II-induced inflammation and mesenchymal transition in vascular endothelium
Authors: Jinfu Qian
Wu Luo
Chengyi Dai
Jun Wang
Xinfu Guan
Chunpeng Zou
Nipon Chattipakorn
Gaojun Wu
Weijian Huang
Guang Liang
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Mar-2021
Abstract: © 2020 Elsevier B.V. Angiotensin II (Ang II)-induced vascular inflammation and injury entails endothelial to mesenchymal transition (EndMT). Recent studies have shown that Ang II engages toll-like receptor 4 (TLR4) in the vasculature to mediate adverse effects. Here, we aimed to investigate whether myeloid differentiation protein 2 (MD2), an extracellular molecule indispensable for TLR4 activation, mediates Ang II-induced vascular injury and EndMT. We utilized MD2 knockout mice and wildtype mice treated with a specific MD2 inhibitor to decipher its role in aortas of Ang II-challenged mice. To confirm our results and to provide mechanistic insights, we exposed cultured endothelial cells to Ang II, with or without MD2 silencing. We show that Ang II causes deleterious remodeling and EndMT in aortas of mice within two weeks. These Ang II effects were largely absent in MD2 knockout mice and in wildtype mice treated with a MD2 inhibitor. MD2 silencing in cultured endothelial cells confirmed the essential role of MD2 in Ang II-induced inflammatory factor induction, and EndMT-associated phenotypic change. We also found that Ang II-MD2-EndMT axis involves the activation of nuclear factor-κB. Our studies highlight an essential role of MD2 in Ang II-induced vascular inflammation and EndMT contributing to vascular injury. These results also imply that MD2 may be targeted to dampen inflammatory cardiovascular and EndMT-associated diseases.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85098570177&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/71827
ISSN: 1879260X
09254439
Appears in Collections:CMUL: Journal Articles

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