Molecular regulation and therapeutic implications of cell death in pulmonary hypertension

Abstract

Pulmonary hypertension (PH) is a clinical and pathophysiological syndrome caused by changes in pulmonary vascular structure or function that results in increased pulmonary vascular resistance and pulmonary arterial pressure, and it is characterized by pulmonary endothelial dysfunction, pulmonary artery media thickening, pulmonary vascular remodeling, and right ventricular hypertrophy, all of which are driven by an imbalance between the growth and death of pulmonary vascular cells. Programmed cell death (PCD), different from cell necrosis, is an active cellular death mechanism that is activated in response to both internal and external factors and is precisely regulated by cells. More than a dozen PCD modes have been identified, among which apoptosis, autophagy, pyroptosis, ferroptosis, necroptosis, and cuproptosis have been proven to be involved in the pathophysiology of PH to varying degrees. This article provides a summary of the regulatory patterns of different PCD modes and their potential effects on PH. Additionally, it describes the current understanding of this complex and interconnected process and analyzes the therapeutic potential of targeting specific PCD modes as molecular targets.