Protective effects of tissue factor pathway inhibitor on mice with lipopolysaccharide-induced acute lung injury

Posum Wan; Kaiheng Gao; Feng Miao; Meng Shi; Xiaofeng Chen

doi:10.1016/j.yexcr.2024.114357

Protective effects of tissue factor pathway inhibitor on mice with lipopolysaccharide-induced acute lung injury

Exp Cell Res. 2024 Nov 25:114357. doi: 10.1016/j.yexcr.2024.114357. Online ahead of print.

Authors

Posum Wan¹, Kaiheng Gao¹, Feng Miao¹, Meng Shi², Xiaofeng Chen³

Affiliations

¹ Department of Thoracic and Cardiovascular Surgery, Huashan Hospital, Aﬃliated with Fudan University, Shanghai 200040, China.
² Department of Thoracic and Cardiovascular Surgery, Huashan Hospital, Aﬃliated with Fudan University, Shanghai 200040, China. Electronic address: mengshi@fudan.edu.cn.
³ Department of Thoracic and Cardiovascular Surgery, Huashan Hospital, Aﬃliated with Fudan University, Shanghai 200040, China. Electronic address: xiaofengchen@fudan.edu.cn.

PMID: 39603553
DOI: 10.1016/j.yexcr.2024.114357

Abstract

Acute lung injury (ALI) resulting from bacterial infection poses a significant risk, and its etiology involves the complex interplay of harmful immune responses and blood coagulation. Despite this understanding, the roles and mechanisms of tissue factor pathway inhibitor (TFPI) in LPS-induced ALI remain insufficiently elucidated. In this study, we aimed to explore the effects of TFPI in LPS-induced ALI. Our investigations revealed that TFPI exerts multiple beneficial effects in LPS-induced ALI. Specifically, TFPI reduces microvascular permeability, Myeloperoxidase (MPO) activity, and cytokine production while inhibiting blood coagulation.Moreover, TFPI demonstrates the capacity to promote proliferation and suppress apoptosis in Human microvascular endothelial cells (HMEC-1) and Human umbilical vein endothelial cells (HUVEC) through the inhibition of the caspase pathway and mitochondrial apoptosis pathway.Furthermore, our findings indicate a correlation between tissue factor (TF) and TFPI expression, with TFPI regulation observed in HMEC-1 cells following LPS treatment. This novel insight suggests that TFPI plays a regulatory role in TF expression. Overall, the protective effect of TFPI on LPS-induced ALI is unveiled by its ability to enhance endothelial cell proliferation and inhibit apoptosis through the modulation of caspase and Bcl-2/Bax pathways. These results underscore the potential of TFPI as a promising therapeutic target for ALI treatment.

Keywords: Acute Lung Injury; Protective Effects; TFPI; lipopolysaccharide; tissue factor.