Circulation Research
17 April 2024
Orphan Nuclear Receptor NR4A3 Promotes Vascular Calcification via Histone Lactylation
Wenqi Ma1,2, Kangni Jia1,2, Haomai Cheng1,2, Hong Xu1, Zhigang Li1,2, Hang Zhang1,2, Hongyang Xie2, Lingfang Zhuang1,2, Ziyang Wang1,2, Yuke Cui1,2, Hang Sun1,2, Lei Yi1,2, Zhiyong Chen1,2, Shengzhong Duan1,3,4, Motoaki Sano5, Keiichi Fukuda5, Lin Lu1,2, Fei Gao6, Ruiyan Zhang1,2, Xiaoxiang Yan1,2
1 Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China.
2 Institute of Cardiovascular Diseases, Shanghai Jiao Tong University School of Medicine, China.
3 Laboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, China.
4 Department of Cardiovascular Medicine, State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China.
5 Department of Cardiology, Keio University School of Medicine, Tokyo, Japan
6 Beijing Anzhen Hospital, Capital Medical University, China
† W. Ma, K. Jia, and H. Cheng contributed equally.
10.1161/CIRCRESAHA.123.323699
Medial arterial calcification is a chronic systemic vascular disorder distinct from atherosclerosis and is commonly observed in patients with chronic kidney disease, diabetes, and aging individuals. Our findings reveal that NR4A3-mediated histone lactylation is a novel metabolome-epigenome signaling cascade mechanism that participates in the pathogenesis of medial arterial calcification.
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