Antirheumatic drug leflunomide attenuates atherosclerosis by regulating lipid metabolism and endothelial dysfunction via DHODH/AMPK signaling pathway
Xinhai Jiang, Weizhi Wang, Lijuan Lei, Tingting Feng, Yang Hu, Peng Liu, Yining Li, Ren Sheng, Yuyan Zhang, Shunwang Li, Jing Zhang, Yuhao Zhang, Zheng Gen Jin, Zhuang Tian, Jian‐Dong Jiang, Yanni Xu, Shuyi Si
Abstract
. Furthermore, leflunomide and its active metabolite teriflunomide suppressed lipid accumulation in free fatty acid (FFA)-induced AML12 cells and improved endothelial dysfunction in palmitic acid (PA)-induced HUVECs through activating AMPK signaling and inhibiting dihydroorotate dehydrogenase (DHODH) signaling pathway. We present evidence that leflunomide and teriflunomide ameliorate atherosclerosis by regulating lipid metabolism and endothelial dysfunction. Our findings suggest a promising use of antirheumatic small-molecule drugs leflunomide and teriflunomide for the treatment of atherosclerosis and related cardiovascular diseases (CVDs).