Tranexamic acid suppresses the release of mitochondrial DNA, protects the endothelial monolayer and enhances oxidative phosphorylation.

Abstract:

:Damage-associated molecular patterns, including mitochondrial DNA (mtDNA) are released during hemorrhage resulting in the development of endotheliopathy. Tranexamic acid (TXA), an antifibrinolytic drug used in hemorrhaging patients, enhances their survival despite the lack of a comprehensive understanding of its cellular mechanisms of action. The present study is aimed to elucidate these mechanisms, with a focus on mitochondria. We found that TXA inhibits the release of endogenous mtDNA from granulocytes and endothelial cells. Furthermore, TXA attenuates the loss of the endothelial monolayer integrity induced by exogenous mtDNA. Using the Seahorse XF technology, it was demonstrated that TXA strongly stimulates mitochondrial respiration. Studies using Mitotracker dye, cells derived from mito-QC mice, and the ActivSignal IPAD assay, indicate that TXA stimulates biogenesis of mitochondria and inhibits mitophagy. These findings open the potential for improvement of the strategies of TXA applications in trauma patients and the development of more efficient TXA derivatives.

journal_name

J Cell Physiol

authors

Prudovsky I,Carter D,Kacer D,Palmeri M,Soul T,Kumpel C,Pyburn K,Barrett K,DeMambro V,Alexandrov I,Brandina I,Kramer R,Rappold J

doi

10.1002/jcp.28603

subject

Has Abstract

pub_date

2019-11-01 00:00:00

pages

19121-19129

issue

11

eissn

0021-9541

issn

1097-4652

journal_volume

234

pub_type

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