Changes in CD4+T Lymphocyte Subsets During the Formation of Hypobaric Hypoxic Pulmonary Artery Hypertension
Objective To investigate changes in lymphocyte subsets in the circulation of patients with hypobaric hypoxic pulmonary artery hypertension(HAPH)and to further clarify changes in lymphocyte subsets at various stages of pulmonary hypertension(PH)formation.Methods An animal model of HAPH was created using a hypobaric hypoxic chamber for rats.Measurements were taken at 3,7,14,21,and 28 days after exposure.Hemodynamic parameters were measured using right heart catheterization,and pulmonary vascular tissue morphology was observed through pathological staining,while changes in CD4+T lymphocyte subsets(Th1,Th2,Th17,Treg)in lung tissue and peripheral circulation were detected using qRT-PCR.Results Compared with the normobaric normoxia control group,levels of Th1,Th2,and Th17 in peripheral circulation were generally proportional to the duration of hypobaric hypoxia,while Treg levels increased from 0 to 7 days,then decreased at 14 days but remained higher than in the normobaric normoxia control group,and further continued to decline at 21 and 28 days to levels lower than the control group.In lung tissue,Th1 levels were significantly higher than in the control group at all time points,without significant differences between groups.Th2 levels increased from 0 to 14 days and then decreased.Th17 levels increased from 0 to 21 days and then decreased.Treg levels decreased from 0 to 7 days,then increased to control levels at 14 days,and further increased at 21 and 28 days.These changes correlated well with the observed progressive thickening of the small pulmonary vessel walls from 0 to 21 days,which showed no significant changes after 21 days.Additionally,tertiary lymphoid organs(TLOs),indicative of chronic immune inflammation,were observed to form,worsen,and stabilize from 0 to 21 days,and tended to stabilize at 28 days.Conclusion Immune-inflammatory mechanisms,particularly the imbalance of lymphocyte subsets,could be involved in the initiation and progression of pulmonary vascular remodeling during HAPH formation.An early anti-inflammatory treatment upon initial exposure to high-altitude environments can serve as a novel preventive measure for HAPH.
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