Programmed cell death: A pivotal player in pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a chronic and progressive pulmonary vascular disease with an extremely high mortality rate. The pathogenesis of PAH is characterized by a progressive increase in vascular resistance due to the excessive proliferation of pulmonary arterial endothelial cells and pulmonary artery smooth muscle cells, which leads to uncompensated remodeling of the right ventricle and, ultimately, right heart failure. However, the molecular mechanisms behind pulmonary arterial hypertension have been much elucidated, but effective therapeutic agents are rare. Programmed cell death (PCD) is an intrinsic cellular process tightly regulated by specific genetic mechanisms, which is usually identified with apoptosis, autophagy, but its scope has been gradually expanded with pyroptosis, ferroptosis, and necroptosis. Both traditional forms of PCD and novel forms have been implicated in the pathogenesis of PAH. In order to gain a more comprehensive understanding of the pathogenesis and progression of PCD in PAH, this review comprehensively summarized the association between various PCDs and PAH and discussed the role of endothelial and smooth muscle cells in this, as well as the crosstalk, which will contribute to the development of innovative and targeted diagnostic and therapeutic approaches.