Wei Zhang,1,* Luofeng Jiang,1,* Xirui Tong,1,* Heng He,1,* Yongjun Zheng,1 Zhaofan Xia1,2 

1Department of Burn Surgery, the First Affiliated Hospital of Naval Medical University, Shanghai, 200433, People’s Republic of China; 2Research Unit of Key Techniques for Treatment of burns and Combined Burns and Trauma Injury, Chinese Academy of Medical Sciences, Shanghai, 200433, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Zhaofan Xia; Yongjun Zheng, Department of Burn Surgery, the First Affiliated Hospital of Naval Medical University, Shanghai, 200433, People’s Republic of China, Email xiazhaofan_smmu@163.com; smmuzhengyongjun@163.com

Abstract: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Endothelial cells (ECs) are an important cell type typically affected in sepsis, resulting in compromised barrier function and various forms of regulated cell death (RCD). However, the precise mechanisms underlying sepsis-induced EC damage remain unclear. This review summarizes the recent research progress on factors and mechanisms that may affect the permeability and RCD of ECs under septic conditions, including glycocalyx, damage-associated molecular patterns, and various forms of RCD in ECs, such as apoptosis, pyroptosis, ferroptosis, and autophagy. This review offers important insights into the underlying mechanisms of endothelial dysfunction in sepsis, aiming to contribute to developing small-molecule targeted clinical therapies.

Keywords: damage-associated protein, endothelial cell, glycocalyx, permeability, regulated cell death, sepsis