Acute lung injury: The therapeutic role of Rho kinase inhibitors

Abstract

Acute lung injury (ALI) is a pulmonary illness with high rates of mortality and morbidity. Rho GTPase and its downstream effector, Rho kinase (ROCK), have been demonstrated to be involved in cell adhesion, motility, and contraction which can play a role in ALI. The electronic databases of Google Scholar, Scopus, PubMed, and Web of Science were searched to obtain relevant studies regarding the role of the Rho/ROCK signaling pathway in the pathophysiology of ALI and the effects of specific Rho kinase inhibitors in prevention and treatment of ALI. Upregulation of the RhoA/ROCK signaling pathway causes an increase of inflammation, immune cell migration, apoptosis, coagulation, contraction, and cell adhesion in pulmonary endothelial cells. These effects are involved in endothelium barrier dysfunction and edema, hallmarks of ALI. These effects were significantly reversed by Rho kinase inhibitors. Rho kinase inhibition offers a promising approach in ALI [ARDS] treatment.

Keywords: Acute lung injury; Endothelial cell; Fasudil; Fasudil (PubChem CID: 3547); Netarsudil (PubChem CID: 66599893); Oleic acid (PubChem CID: 445639); Paraquat (PubChem CID: 15939); ROCK; Rho kinase inhibitor; Ripasudil (PubChem CID: 9863672); Simvastatin (PubChem CID: 54454); Y-27632 (PubChem CID: 9901617).