Abstract
C1q/TNF-related protein 9 (CTRP9) is implicated in diverse cardiovascular diseases, but its role in viral myocarditis (VMC) is not well explored. This study is aimed at investigating the role and potential mechanism of CTRP9 in VMC. Herein, we found that the peripheral blood collected from children with VMC had lower CTRP9 levels than that from children who had recovered from VMC. H9c2 cardiomyocytes treated with coxsackievirus B3 (CVB3) were applied to establish a VMC model in vitro, and the expression of CTRP9 was significantly decreased in CVB3-induced H9c2 cells. The overexpression of CTRP9 attenuated CVB3-induced apoptosis, inflammation, and fibrosis reactions in H9c2 cells by promoting cell proliferation, reducing the cell apoptosis rate, and inhibiting inflammatory cytokine levels and fibrosis-related gene expression. Moreover, we found that thrombospondin 1 (THBS1) levels were increased in children with VMC, and CTRP9 negatively regulated THBS1 expression by interacting with THBS1. The downregulation of THBS1 inhibited CVB3-induced apoptosis, inflammation, and fibrosis in H9c2 cells. In addition, our mechanistic investigation indicated that the overexpression of THBS1 impaired the inhibitory effect of CTRP9 on CVB3-induced H9c2 cells. The results further revealed that the CVB3-induced NF-κB and TGF-β1/Smad2/3 signaling pathways of H9c2 cells were blocked by CTRP9 yet activated by THBS1. In conclusion, CTRP9 protected H9c2 cells from CVB3-induced injury via the NF-κB and TGF-β1/Smad2/3 signaling pathways by modulating THBS1.
Highlights
Viral myocarditis (VMC) is a common cardiovascular disease in the clinic [1]
To clarify the role of C1q/TNF-related protein 9 (CTRP9) in pediatric viral myocarditis (VMC), the expression of CTRP9 mRNA and protein in the serum of children with VMC was detected by Quantitative Real-Time PCR (qRT-PCR) and Enzyme-Linked Immunosorbent Assay (ELISA)
Our data showed that children with VMC have lower CTRP9 levels than children who have recovered from VMC, suggesting that CTRP9 might play a role in VMC (Figures 1(a) and 1(b), P < 0:05)
Summary
Viral myocarditis (VMC) is a common cardiovascular disease in the clinic [1]. It is localized or diffuse myocarditis caused by viral infection, which can cause localized or extensive myocardial interstitial inflammatory infiltration and myocardial cell necrosis or apoptosis, eventually leading to irreversible cardiac dysfunction [2]. Transforming growth factor- (TGF-) β1 is one of the most important precipitating factors in tissue fibrosis [9]. It affects the expression of extracellular matrix proteins by activating the downstream
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