Protective effects of adipose-derived biogenic nanoparticles on the pulmonary microvascular endothelial barrier in mice with ventilator-induced lung injury via the TRPV4/ROCK1 signalling pathway.

Abstract

PURPOSE:

The "obesity paradox" phenomenon occurs in critically ill patients who receive mechanical ventilation. Our previous studies found that the adipose-derived exosomes secreted by obese mice have a protective effect on the pulmonary microvascular endothelial barrier. However, the extraction of exosomes is cumbersome, their yield is low, and their storage is difficult. After further research, we discovered a new type of adipose-derived bioactive material called: lipoaspirate nanoparticles (Lipo-NPs).

METHODS:

Lipo-NPs were extracted and identified using a tangential flow filtration system. The Lipo-NPs were used as an intervention in ventilator-induced lung injury (VILI) models in vivo and in vitro to investigate whether they have a protective effect on lung tissue damage (haematoxylin and eosin staining), lung barrier function (lung wet/dry [W/D] weight ratio, protein concentration in bronchoalveolar lavage fluid (BALF), and Vascular endothelial (VE)-expression), as well as their related mechanisms.

RESULTS:

In both in vivo and in vitro studies, Lipo-NPs can attenuate lung injury, reduce lung W/D ratio and protein concentration in BALF, and augment the expression of the adhesion link-protein VE-cadherin, thus playing a protective role in lung barrier function. This protective effect involves the activation of the transient receptor potential vanilloid 4 (TRPV4)/Rho-associated kinase1 (ROCK1) signalling pathway. We further verified the role of this signalling pathway via activation and inhibition of TRPV4 and ROCK1. Moreover, phosphorylation of myosin light chain 2 (MLC2) regulates F-actin and is a target of the ROCK pathway.

CONCLUSION:

Lipo-NPs can enhance the expression of VE-cadherin by inhibiting the TRPV4/ROCK1/pMLC2 signalling pathway in the mechanical ventilation model, thereby exerting a protective effect on the VILI pulmonary microvascular endothelial barrier.

• Authors: Qian Yu, Daoxin Wang, Shulei Fan, Xumao Tang, Jing He, Junnan Peng, Di Qi
• Journal: Pulmonary pharmacology & therapeutics (Pulm Pharmacol Ther) Vol. 73-74 Pg. 102123 (06 2022) ISSN: 1522-9629 [Electronic] England
• PMID: 35306165 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier Ltd. All rights reserved.

Chemical References

• TRPV Cation Channels
• Trpv4 protein, mouse
• Rock1 protein, mouse
• rho-Associated Kinases

Topics

• Animals
• Humans
• Lung (metabolism)
• Mice
• Mice, Inbred C57BL
• Nanoparticles
• Respiration, Artificial
• TRPV Cation Channels (metabolism)
• Ventilator-Induced Lung Injury (prevention & control)
• rho-Associated Kinases (metabolism)