Bingming Peng, Yingzhen Zhou, Xingmeng Fu, Li Chen, Zhengxia Pan, Qijian Yi, Tengteng Zhao, Zhou Fu, Ting Wang
Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders and Ministry of Education Key Laboratory of Child Development and Disorders. University of California, San Diego.
China and United States
Pulmonary Circulation
Pulm Circ 2024; 14:
DOI: 10.1002/pul2.70019
Abstract
Long-term hypoxia is one of the main causes of pulmonary vascular remodeling in pulmonary hypertension (PH) associated with congenital heart disease (CHD) children. Endothelial to mesenchymal transition (EndMT) is an important pathological basis of pulmonary vascular remodeling in PH. We observed that Fibronectin 1 (FN1) had strong protein-protein interactions with both Thrombospondin 1 (THBS1) and Transglutaminase 2 (TGM2) in PH with venous peripheral bloods samples from pediatric patients and healthy children. LungMAP CellCards and heatmaps of human PAEC in PH patients and lung tissues in hypoxia induced PH mice model were used to show that THBS1 and FN1 were significantly elevated. We studied the relationship between THBS1 and FN1 in vivo, by using SUHX-induced PH mice model, and in vitro, by using hypoxia-induced human PAEC. The results showed that hypoxia could result in EndMT and inhibiting THBS1 could reverse EndMT in vivo and in vitro, verifying our transcriptome results. Taken together, our research demonstrated that THBS1 could mediate hypoxia driven EndMT of PH, providing a new insight of research in the pathophysiology of PH.
Category
Class III. Pulmonary Hypertension Associated with Alveolar Hypoxia
Vascular Cell Biology and Mechanisms of Pulmonary Vascular Disease
Animal Models of Pulmonary Vascular Disease and Therapy
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