PFKFB3-mediated endothelial glycolysis promotes pulmonary hypertension

• DOI: 10.1073/pnas.1821401116
• Publication Date: 2019-06-18T21:25:17Z
• Authors: Yapeng Cao; Xiaoyu Zhang; Lina Wang; Qiuhua Yang; Qian Ma; Jiean Xu; Jingjing Wang; Laszlo Kovacs; Ramon J. Ayon; Zhiping Liu; Min Zhang; Yaqi Zhou; Xianqiu Zeng; Yiming Xu; Yong Wang; David J. Fulton; Neal L. Weintraub; Rudolf Lucas; Zheng Dong; Jason X.-J. Yuan; Jennifer C. Sullivan; Louise Meadows; Scott A. Barman; Chaodong Wu; Junmin Quan; Mei Hong; Yunchao Su; Yuqing Huo
• Keywords: Metabolic pathway

Significance Lung endothelial cells express high levels of glucose metabolic enzymes, such as PFKFB3, and consequently produce large amounts metabolites. These metabolites are able to stabilize the cell signaling molecule HIF2A, similar that which occurs under hypoxic conditions. This stabilization HIF2A by in lung stimulates production growth inflammatory factors, thereby enhancing proliferation inflammation pulmonary vessels exacerbating hypertension (PH). In this study, blockade PFKFB3 inhibits PH development rodent models, suggesting targeting enzymes is a promising strategy for treatment PH.