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
Affiliations
Wenjuan Mu
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
Shuwen Qian
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
Yanjue Song
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
Lijie Yang
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
Saisai Song
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
Qiqi Yang
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
Hao Liu
Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiaotong University of Medicine College, Shanghai 200032, China
Yang Liu
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
Dongning Pan
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
Yan Tang
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; Corresponding author. Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Yi xue yuan Road, Shanghai 200032, PR China.
Qi-Qun Tang
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; Corresponding author. Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Yi xue yuan Road, Shanghai 200032, PR China.
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.
