Pulmonary artery smooth muscle cell pyroptosis promotes the proliferation of PASMCs by paracrine IL‑1β and IL‑18 in monocrotaline‑induced pulmonary arterial hypertensive rats

Pulmonary arterial hypertension (PAH) is a common vascular disease, and pulmonary vascular remodeling is a pivotal pathophysiological mechanism of PAH. Major pathological changes of pulmonary arterial remodeling, including proliferation, hypertrophy and enhanced secretory activity, can occur in pulmonary artery smooth muscle cells (PASMCs). Multiple active factors and cytokines play important roles in PAH. However, the regulatory mechanisms of the active factors and cytokines in PAH remain unclear. The present study aimed to reveal the crucial role of PASMC Pyroptosis in PAH and to elucidate the intrinsic mechanisms. To establish the PAH rat models, Sprague-Dawley rats were injected intraperitoneally with monocrotaline (MCT) at a dose of 60 mg/kg. The expression of proteins and interleukins were detected by western blotting and ELISA assay. The results indicated that the Pyroptosis of PASMCs is significantly increased in MCT-induced PAH rats. Notably, pyroptotic PASMCs can secret IL-1β and IL-18 to promote the proliferation of PASMCs. On this basis, inhibiting the secretion of IL-1β and IL-18 can markedly inhibit PASMC proliferation. Collectively, the findings of the present study indicate a critical role for PASMC Pyroptosis in MCT-induced PAH rats, prompting a new preventive and therapeutic strategy for PAH.

gasdermin D; interleukin 18; interleukin 1β; pulmonary arterial hypertension; pulmonary artery smooth muscle cells; pyroptosis.