Fasudil exerts a cardio‐protective effect on mice with coxsackievirus B3‐induced acute viral myocarditis

Abstract

Summary Aims To investigate whether there exists a cardio‐protective effect of Fasudil, a selective Rho kinase (ROCK) inhibitor, in an experimental murine model of acute viral myocarditis. Methods Male BALB/c mice were randomly assigned to three groups: control, myocarditis treated with placebo and myocarditis treated with Fasudil (n = 40 animals per group). Myocarditis was established by intraperitoneal injection with coxsackievirus B3 (CVB3). Twenty‐four hours after infection, Fasudil was intraperitoneally administered for 14 consecutive days. Twenty mice were randomly selected from each group to monitor a 14‐day survival rate. On day 7 and day 14, eight surviving mice from each group were sacrificed and their hearts and blood were obtained to perform serological and histological examinations. Expression of ROCKs, IL‐17, IL‐1b, TNFα, RORgt, and Foxp3 were quantified with RT‐PCR. Plasma levels of TNF alpha, IL‐1 beta, and IL‐17 were measured by ELISA. In addition, protein levels of IL‐17 and ROCK2 in cardiac tissues were analyzed with Western blot. Results Fasudil treatment significantly increased survival, attenuated myocardial necrotic lesions, reduced CVB3 replication and expression of ROCK2 and IL‐17 in the infected hearts. This treatment also imposed a T‐cell subpopulation shift, from Th17 to Treg, in cardiac tissues. Conclusions ROCK pathway inhibition was cardio‐protective in viral myocarditis with increased survival, decreased viral replication, and inflammatory response. These findings suggest that Fasudil might be a potential therapeutic agent for patients with viral myocarditis.

Ablation of RhoA impairs Th17 cell differentiation and alleviates house dust mite-triggered allergic airway inflammation

“…In addition, RhoA functions through activation of its immediate downstream effectors such as Rho‐associated protein kinase (ROCK), mDia, and protein kinase N . Blockade of ROCK activity by its specific inhibitors Y27632 or fasudil is associated with the downregulation of Th17 function and improvement for several autoimmune and inflammatory diseases, such as systemic lupus erythematosus, OVA‐induced murine allergic lung inflammation, and viral myocarditis . Thus, ROCK likely contributes to RhoA‐regulated Th17 signaling and differentiation.…”

Ginkgo biloba extract may alleviate viral myocarditis by suppression of S100A4 and MMP‐3

“…As anticipated, the mRNA and protein levels of S100A4 were found to be significantly reduced after the application of Ginkgo biloba extract, which has not been reported previously and thus may be a novel theory. Furthermore, viral replication is the initiating factor of CVB 3 ‐induced myocarditis and therefore, blocking viral replication may be the first aim for treatment of VMC . Previously, the inhibitory effect of Ginkgo biloba extract had been observed against influenza A, B viruses and human immunodeficiency virus‐1 .…”

“…Furthermore, viral replication is the initiating factor of CVB 3 -induced myocarditis and therefore, blocking viral replication may be the first aim for treatment of VMC. 43,44 Previously, the inhibitory effect of Ginkgo biloba extract had been observed against influenza A, B viruses 45 and human immunodeficiency virus-1. 46 Hereby, Ginkgo biloba extract may also have the potential to reduce viral burden of CVB 3 .…”

Inhibition of Rho-Kinase Downregulates Th17 Cells and Ameliorates Hepatic Fibrosis by Schistosoma japonicum Infection

“…Fasudil may also inhibit Th17 cells. Fasudil treatment was related to the downregulation of IL-17 mRNA expression from cardiac tissues in a murine model of myocarditis [24]. Y27632, another RhoA-ROCK inhibitor, can suppress ovalbumin (OVA)-induced murine asthma with reduced IL-17 mRNA expression in lungs [25].…”