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J Mol Cell Cardiol. 2018 Dec;125:50-60. doi: 10.1016/j.yjmcc.2018.10.015. Epub 2018 Oct 17.

Central role of RIPK1-VDAC1 pathway on cardiac impairment in a non-human primate model of rheumatoid arthritis.

Author information

1
Institute of Molecular Medicine, Peking University, Beijing 100871, China; Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China; Department of Rheumatology, Dazhou Central Hospital, Dazhou 635000, China.
2
Institute of Molecular Medicine, Peking University, Beijing 100871, China; Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China.
3
Department of Radiology, The PLA General Hospital of Air Force, No. 30, Fucheng Road, Beijing 100142, China.
4
Department of Ultrasound, Fuwai Hospital, Beijing 100037, China.
5
Institute of Molecular Medicine, Peking University, Beijing 100871, China; Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China; State Key Laboratory of Biomembrane and Membrane Biotechnology, Peking-Tsinghua Center for Life Sciences, Beijing 100871, China.
6
Institute of Molecular Medicine, Peking University, Beijing 100871, China; Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing 100871, China. Electronic address: zhangxq@pku.edu.cn.

Abstract

Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by destructive polyarthritis and systemic complications. It increases cardiovascular morbidity and mortality. However, the mechanism underlying RA-related cardiac damage remains largely unknown. Here, we found and characterized a non-human primate (NHP) model with spontaneous RA similar to the human conditions. Compared with the control group, the cardiac function in RA monkeys showed progressively deterioration; histologically, we found significantly increased inflammatory cell infiltration, cell death, and fibrosis in RA monkey heart tissue. Mechanistically, the upregulated receptor-interacting protein kinase 1 (RIPK1) in RA monkey heart tissue bound to voltage-dependent anion-selective channel 1 (VDAC1), increased VDAC1 oligomerization, and subsequently induced cardiac cell death and functional impairment. These findings identified that RIPK1-VDAC1 pathway is a promising target to treat cardiac impairment in RA. This unique model of RA will provide a valuable tool for mechanistic and translational studies.

KEYWORDS:

Cardiovascular disease; Inflammation; Non-human primate; Receptor-interacting protein kinase 1; Rheumatoid arthritis; Voltage-dependent anion-selective channel protein 1

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