Search

CVB3 virus tropism and tissue access are modulated by cardiac microvascular endothelial cells (CMVECs) in the context of microvasculature. This study was designed to examine biological behaviors of CMVECs following CVB3 infection and its possible effects on cardiac remodeling. Data demonstrated that CVB3 increased caspase-3 activities, Bax/Bcl-2 protein ratio and TGF-β1 levels in CMVECs, accompanying with elevated microvascular permeability. Double immunofluorescence revealed co-localization of endothelial markers (CD31 and VE-cadherin) and mesenchymal markers (FSP1 and αSMA) in infected CMVECs. Western blot demonstrated that CVB3 significantly decreased the expression of endothelial markers and increased the expression of mesenchymal markers, which were reversed by SB431542 (inhibitor of TGF-β1), indicating that endothelial-to-mesenchymal transition following CVB3 infection was probably induced by CMVECs-derived TGF-β1. Excess extracellular matrix was produced by myocardial cells incubated with supernatants of infected CMVECs. Our results displayed that CVB3 induced notable biological changes of CMVECs, which may contribute to cardiac fibrosis., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Myocardial fibrosis plays an important role in coxsackievirus B3 (CVB3) induced dilated cardiomyopathy. Excessive transforming growth factor (TGF)-β1 contributes to a pathologic excess of tissue fibrosis. We investigated the effect of astragaloside IV on myocardial fibrosis in CVB3-induced dilated cardiomyopathy. BALB/c mice were inoculated with CVB3 to induce acute viral myocarditis on day 7 (acute VMC group), monthly for 3 months to induce chronic myocarditis (chronic VMC group), and monthly for 9 months to induce dilated cardiomyopathy (DCM group). The same method was used for the DCM+Astra group as that of the DCM group, but former group was given with astragaloside IV-containing drinking water. Compared to DCM group, astragaloside IV treatment significantly increased the survival rate. Histological findings and the collagen volume fraction showed that astragaloside IV decreased fibrosis in heart tissues. Astragaloside IV decreased the level of the serum carboxy-terminal propeptide of procollagen type I (PICP) and the ratio of PICP/ N-terminal type I procollagen propeptide (PINP). Ameliorated myocardial fibrosis was consistent with the downregulated expression of TGF-β1 and its downstream pSmad2/3 and Smad4 in the myocardium of the DCM+Astra group compared to the DCM group. The level of type I collagen was lower in the DCM+Astra group than the DCM group. The same effect was found in the in vitro study. These findings showed that astragaloside IV had a potent preventive effect on myocardial fibrosis in CVB3-induced dilated cardiomyopathy that might be due to downregulation of TGF-β1-Smad signaling., (Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Inflammation is thought to be important in mediating the progression of chronic heart failure (CHF). Whether beneficial effects on inflammation can be achieved by statins in patients with CHF remains uncertain. This meta-analysis was conducted to determine the role of statin therapy in inflammation markers in CHF patients., Methods: Pubmed, MEDLINE, EMBASE, and EBM Reviews databases were searched for randomized controlled trials comparing statin treatment with non-statin treatment in CHF patients. Two reviews independently assessed studies and extracted data. Standardized mean differences (SMD) were calculated using random effects models., Results: Ten studies with 6052 patients were included. Pooled analysis showed that statin therapy was associated with significant decrease in high-sensitivity C-reactive protein (SMD = -0.74, 95% CI -1.16 to -0.32; p = 0.0005) and soluble vascular cell adhesion molecule-1 (SMD = -0.49, 95% CI -0.91 to -0.08; p = 0.02). However, the beneficial effects of statin were not shown regarding interleukin-6 (SMD = -0.85, 95% CI -2.09 to 0.38; p = 0.18) and tumor necrosis factor-α (SMD = -0.13, 95% CI -0.50 to 0.25; p = 0.51). Sources of heterogeneity were not found by meta-regression analyses, whereas subgroup analyses showed that difference in age, etiology, baseline left ventricular ejection fraction, type of statins and follow-up duration might influence the effects of statins., Conclusions: Statin may partially suppress inflammatory markers in patients with CHF; moreover, this beneficial effect may be associated with different types of statins, treatment intervals and characteristics of patients., (Copyright © 2010 IMSS. Published by Elsevier Inc. All rights reserved.)

Myocarditis is associated with increased number of CD4+ T cells in the myocardium after coxsackievirus B3 (CVB3) infection. Previous studies show that CD11c+ myeloid dendritic cells (mDC) loaded with myosin could induce myocarditis. This study aims to investigate the generation and accumulation of mDC in CVB3-induced myocarditis. The presence of mDC in myocardium was detected by immunohistochemisty. Bone marrow-derived mDC were generated from uninfected and CVB3-infected mice. The percentage of CD11c+ mDC on cultured cells and mean fluorescence index (MFI) of double positive cells (CD11c+CD40+, CD11c+CD80+) were measured by flow cytometry. The expression of chemokine receptors (CCR5, CCR7) on mDC and chemokines (CCL4, CCL19) in the myocardium was detected. The migration of mDC in response to CCL4 or CCL19 was measured by chemotaxis assay. Mature mDC were elevated in the myocardium from CVB3-infected mice. The percentage of mDC generated from CVB3-infected group was increased. The MFI of CD11c+CD40+ and CD11c+CD80+ was increased in CVB3-infected group. The mDC showed a down-regulation of CCR5 and unaffected CCR7 mRAN levels associated with elevated CCL4 and CCL19 in the myocardium in CVB3-infected group. Numbers of migrating bone marrow-derived mDC from CVB3-infected mice were increased in vitro. We conclude that CVB3 infection induced the greater generation of mDC from bone marrow and accumulation of mature mDC in myocardial tissues. This migration was associated with increased levels of both CCL4 and CCL19 in the heart tissue. These suggest that blocking the migration of mDC may provide a novel therapy for myocarditis.