Jin Shentu, Wenxuan Dai, Chang Chen, Jiawei Huang, Lijun Chen, Yi Yan, Han Zhang, Zhongqun Zhu, Guocheng Shi, Huiwen Chen
Shanghai Children’s Medical Center and Shanghai Jiao Tong University School of Medicine.
China
Journal of Thoracic and Cardiovascular Surgery
J Thorac Cardiovasc Surg 2026;
DOI: 10.1016/j.jtcvs.2026.01.017
Abstract
Objectives: Group 2 pulmonary hypertension (PH) remains a highly morbid disease, yet no specific therapy exists. We sought to determine whether total pulmonary vein banding (TPVB) in rats could reliably display the clinical features of group 2 PH, and sought to investigate potential molecular and cellular determinants associated with disease progression.
Methods: Four-week-old Sprague-Dawley rats were randomized to receive TPVB (n=18) or sham procedure (n=18). Serial hemodynamic and histological assessments were performed at post-TPVB week 1, 4, and 8. At each time point, 12 rats (6 in TPVB vs. 6 in sham group) underwent harvest for lung sectioning and transcriptomic and proteomic analysis. Weighted gene coexpression and Bayesian networks were used to explore the top hub gene associated with PH development.
Results: Comparing to the sham group, rats in the TPVB group developed PH after surgery. Mild to severe progression of PH was observed in the TPVB group from post-surgery week 1 to 8, including higher right ventricular systolic pressure (P < 0.001), impaired right ventricle (RV)-pulmonary artery coupling (P < 0.001), decreased tricuspid annular plane systolic excursion (P < 0.001) and RV fractional area change (P < 0.001). Slc2a1 was identified as a hub gene upregulated in the lungs, which was enriched in the perivascular macrophages and associated with disease progression.
Conclusions: Rodent model of TPVB provides a useful platform for modeling PV-congestion severe group 2 PH. Slc2a1 is a key regulator of perivascular macrophage infiltration, driving the disease progression. Targeting Slc2a1-mediated perivascular inflammation might have a therapeutic potential.
Category
Stenosis or Obstruction of Normal Pulmonary Venous Connections
Pulmonary Hypertension Associated with Stenosis or Atresia of Pulmonary Veins
Pulmonary Venous Pathology
Other Factors Influencing the Onset, Severity or Outcome of Disease: Inflammation
Year of Publication: 2026
Age Focus: Pediatric
Article Type: Animal Models of Disease and Therapy
Article Access: Free PDF File or Full Text Article Available Through PubMed or DOI: Yes