New insights into pulmonary arterial hypertension: interaction between PANoptosis and perivascular inflammatory responses

Pulmonary arterial hypertension (PAH) is a heterogeneous disease characterized by various etiologies, with pulmonary vascular remodeling recognized as a main pathological change. Currently, it is widely accepted that vascular remodeling is closely associated with abnormal pulmonary vascular cell death and perivascular inflammation. The simultaneous activation of various pulmonary vascular cell death leads to immune cell adhesion and inflammatory mediator releases; And in turn, the inflammatory response may also trigger cell death and jointly promote the progression of vascular remodeling. Recently, PANoptosis has been identified as a phenomenon that describes the simultaneous activation and interaction of multiple forms of programmed cell death (PCD). Therefore, the relationship between PANoptosis and inflammation in PAH warrants further investigation. This review examines the mechanisms underlying apoptosis, necroptosis, pyroptosis, and inflammatory responses in PAH, with a focus on PANoptosis and its interactions with inflammation. And it aims to elucidate the significance of this emerging form of cell death and inflammation in the pathophysiology of PAH and to explore its potential as a therapeutic target.