Fig. 1: The evolution of the PCD concept.
From: Research advances on the role of programmed endothelial cell death in sepsis
Following biologists’ observations of cell death phenomena, distinct forms of programmed cell death (PCD) have been successively identified, including apoptosis (1972), pyroptosis (1992), necroptosis (2000), and ferroptosis (2012), among others. The key regulatory molecules and mechanisms underlying these processes were gradually elucidated, revealing their interconnected nature rather than independence. This culminated in the proposal of PANoptosis in 2019, emphasizing the integration of multiple PCD pathways. Concurrently, endothelial cells' (ECs) PCD has been recognized as pivotal in sepsis pathogenesis. Recent guidelines (2019) for the first time incorporated “endothelial protection” into sepsis management, and targeting ECs’ PCD mechanisms has emerged as a key focus in current therapeutic research.
