Yao Yao, Xin Bin, Yanxuan Xu, Shaowan Chen, Si Chen, Xiang-Ling Yuan, Yingjie Cao, Tsz Kin Ng
Beijing Children’s Hospital, Capital Medical University and National Center for Children’s Health. Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College. Beijing Children’s Hospital and Capital Medical University. Chinese Academy of Sciences. Peking University Health Science Center.
China
Cell Proliferation
Cell Prolif 2024;
DOI: 10.1111/cpr.13717
Abstract
Aerobic glycolysis is involved in the pathogenesis of pulmonary hypertension (PH). The mechanisms by which glycolysis is increased and how it contributes to pulmonary vascular remodelling are not yet fully understood. In this study, we demonstrated that elevated lipocalin-2 (LCN2) in PH significantly enhances aerobic glycolysis in human pulmonary artery smooth muscle cells (PASMCs) by up-regulating LDHA expression. Knockout of Lcn2 or having heterozygous LDHA deficiency in mice significantly inhibits the progression of hypoxic PH. Our study reveals that LCN2 stimulates LDHA expression by activating Akt-HIF-1α signalling pathway. Inhibition of Akt or HIF-1α reduces LDHA expression and proliferation of PASMCs. Both Akt and HIF-1α play critical roles in the development of PH and are suppressed in the pulmonary vessels of hypoxic PH mice lacking LCN2. These findings shed light on the LCN2-Akt-HIF1α-LDHA axis in aerobic glycolysis in PH.
Category
Class III. Pulmonary Hypertension Associated with Alveolar Hypoxia
Animal Models of Pulmonary Vascular Disease and Therapy
Vascular Cell Biology and Mechanisms of Pulmonary Vascular Disease
Age Focus: No Age-Related Focus
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes