BMP4-mediated browning of perivascular adipose tissue governs an anti-inflammatory program and prevents atherosclerosis

Wenjuan Mu; Shuwen Qian; Yanjue Song; Lijie Yang; Saisai Song; Qiqi Yang; Hao Liu; Yang Liu; Dongning Pan; Yan Tang; Qi-Qun Tang

doi:10.1016/j.redox.2021.101979

BMP4-mediated browning of perivascular adipose tissue governs an anti-inflammatory program and prevents atherosclerosis

Redox Biol. 2021 Jul:43:101979. doi: 10.1016/j.redox.2021.101979. Epub 2021 Apr 17.

Authors

Wenjuan Mu¹, Shuwen Qian¹, Yanjue Song¹, Lijie Yang¹, Saisai Song¹, Qiqi Yang¹, Hao Liu², Yang Liu¹, Dongning Pan¹, Yan Tang³, Qi-Qun Tang⁴

Affiliations

¹ Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences and Department of Endocrinology and Metabolism of Zhongshan Hospital, Fudan University, Shanghai 200032, China.
² Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiaotong University of Medicine College, Shanghai 200032, China.
³ Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences and Department of Endocrinology and Metabolism of Zhongshan Hospital, Fudan University, Shanghai 200032, China. Electronic address: yantang@fudan.edu.cn.
⁴ Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology of School of Basic Medical Sciences and Department of Endocrinology and Metabolism of Zhongshan Hospital, Fudan University, Shanghai 200032, China. Electronic address: qqtang@shmu.edu.cn.

Abstract

Loss of perivascular adipose tissue (PVAT) impairs endothelial function and enhances atherosclerosis. However, the roles of PVAT thermoregulation in vascular inflammation and the development of atherosclerosis remains unclear. Bone morphogenetic protein 4 (BMP4) transforms white adipocyte to beige adipocyte, while promotes a brown-to-white shift in inter-scapular brown adipose tissue (BAT). Here, we found that knockdown of BMP4 in PVAT reduced expression of brown adipocyte-characteristic genes and increased endothelial inflammation in vitro co-culture system. Ablating BMP4 expression either in adipose tissues or specifically in BAT in ApoE^-/- mice demonstrated a marked exacerbation of atherosclerotic plaque formation in vivo. We further demonstrated that proinflammatory factors (especially IL-1β) increased in the supernatant of BMP4 knockdown adipocytes. Overexpression of BMP4 in adipose tissues promotes browning of PVAT and protects against atherosclerosis in ApoE^-/- mice. These findings uncover an organ crosstalk between PVAT and blood endothelial cells that is engaged in atherosclerosis.

Keywords: Atherosclerosis; Browning; Inflammation; Lipid metabolism; Perivascular adipose tissue.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipose Tissue
Adipose Tissue, Brown
Adipose Tissue, White
Animals
Anti-Inflammatory Agents
Atherosclerosis*
Bone Morphogenetic Protein 4
Endothelial Cells*
Mice

Substances

Anti-Inflammatory Agents
Bmp4 protein, mouse
Bone Morphogenetic Protein 4