Preprint Article Version 1 This version is not peer-reviewed

Fasudil Attenuates LPS-Induced Acute Lung Injury by Preventing Endothelial Dysfunction

These authors contributed equally to this work
Version 1 : Received: 30 March 2017 / Approved: 31 March 2017 / Online: 31 March 2017 (08:30:54 CEST)

How to cite: Wang, J.; Xu, J.; Zhao, X.; Xie, W.; Wang, H.; Kong, H. Fasudil Attenuates LPS-Induced Acute Lung Injury by Preventing Endothelial Dysfunction. Preprints 2017, 2017030225 (doi: 10.20944/preprints201703.0225.v1). Wang, J.; Xu, J.; Zhao, X.; Xie, W.; Wang, H.; Kong, H. Fasudil Attenuates LPS-Induced Acute Lung Injury by Preventing Endothelial Dysfunction. Preprints 2017, 2017030225 (doi: 10.20944/preprints201703.0225.v1).

Abstract

Fasudil, a potent Rho kinase (ROCK) inhibitor, can ameliorate LPS-induced acute lung injury (ALI) in mice, but the mechanism remains obscure. In this study, a mice model of ALI was established by intra-tracheal instillation of LPS. Histological changes, cytokine levels, lung permeability, and endothelial apoptosis were determined to evaluate the effects of fasudil on lung injury. The cellular and molecular biological mechanisms were explored by culturing human pulmonary microvascular endothelial cells (PMECs). The results showed that fasudil reduced LPS-induced lung inflammation, pulmonary hyperpermeability, and endothelial apoptosis in mice. In cultured human PMECs, fasudil inhibited LPS-induced caspse-3 cleavage and cell apoptosis. It also decreased LPS-induced hyperpermeability of human PMECs monolayer by reversing the down-regulation of intercellular junctions. Moreover, fasudil inhibited LPS-induced overexpression of chemokines and intercellular adhesion molecule (ICAM)-1 in human PMECs, which in turn suppressed neutrophil chemotaxis and neutrophil-endothelial adhesion. Further molecular researches showed fasudil inhibited LPS-induced activation of ROCK, NF-κB, and p38 in human PMECs. Our findings demonstrated that fasudil alleviated LPS-induced ALI by protecting endothelial function via inhibiting endothelial apoptosis, maintaining endothelial barrier integrity, and reducing endothelial inflammation. These effects of fasudil could be attributed to the inhibition of ROCK and its downstream NF-κB and p38 signaling pathways.

Subject Areas

acute lung injury; fasudil, Rho kinase; endothelial function; inflammation

Readers' Comments and Ratings (0)

Leave a public comment
Send a private comment to the author(s)
Rate this article
Views 0
Downloads 0
Comments 0
Metrics 0
Leave a public comment

×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.