Pyroptosis is a pro-inflammatory form of programmed cell death, whose genesis 
directly depended on caspase-1 activation. Pulmonary hypertension (PH) is a 
disease characterized, in part, by vascular fibrosis. Up to now, there is no 
report on the relationship between pyroptosis and vascular fibrosis in PH. Here, 
we confirmed that pyroptosis had occurred in the media of pulmonary arteries in 
two PH rat models and hypoxic human pulmonary arterial smooth muscle cells 
(hPASMCs). Caspase-1 inhibition attenuated the pathogenesis of PH, as assessed 
by vascular remodeling, right ventricular systolic pressure, right ventricle 
hypertrophy and hemodynamic parameters of pulmonary vasculature. Moreover, 
caspase-1 inhibition suppressed pulmonary vascular fibrosis as demonstrated by 
Masson staining, as well as immunohistochemistry and Western blot analysis of 
fibrillar collagen. In addition, Programmed death-ligand 1 (PD-L1) was markedly 
increased in PH, which was regulated by the transcription factor STAT1. 
Furthermore, PD-L1 knockdown in hPASMCs repressed the onset of hypoxia-induced 
pyroptosis and fibrosis. Overall, these data identify a critical STAT1-dependent 
posttranscriptional modification that promotes PD-L1 expression in the 
pyroptosis of PASMCs to modulate pulmonary vascular fibrosis and accelerate the 
progression of PH.