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Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by recurrent coma, ventricular tachycardias and the replacement of the myocardium with fatty and fibrous tissue. We described a 42-year-old female patient without clinical arrhythmias which was diagnosed as ARVC by magnetic resonance imaging (MRI), but the transvenous endomyocardial biopsy was not specific. The patient received heart transplantation due to her refractory heart failure and the pathology of explanted heart demonstrated typical replacement of fatty and fibrous tissue and piles of infiltrated lymphocytes in myocardial tissue. It is concluded that ARVC might not have any arrhythmias and inflammatory process may be involved in the mechanism of ARVC. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) are small, noncoding RNA molecules of 20 to 22 nucleotides that regulate gene expression by binding to their 3' untranslated region (3'UTR). Increasing data implicate altered miRNA participation in the progress of cancer. We previously reported that CYP2J2 epoxygenase promotes human cancer phenotypes. But whether and how CYP2J2 is regulated by miRNA is not understood. Methods and Results: Using bioinformatics analysis, we found potential target sites for miRNA let-7b in 39UTR of human CYP2J2. Luciferase and western blot assays revealed that CYP2J2 was regulated by let-7b. In addition, let-7b decreased the enzymatic activity of endogenous CYP2J2. Furthermore, let-7b may diminish cell proliferation and promote cell apoptosis of tumor cells via posttranscriptional repression of CYP2J2. Tumor xenografts were induced in nude mice by subcutaneous injection of MDA-MB-435 cells. The let-7b expression vector, pSilencer-let-7b, was injected through tail vein every 3 weeks. Let-7b significantly inhibited the tumor phenotype by targeting CYP2J2. Moreover, quantitative real-time polymerase chain reaction and western blotting were used to determine the expression levels of let-7b and CYP2J2 protein from 18 matched lung squamous cell cancer and adjacent normal lung tissues; the expression level of CYP2J2 was inversely proportional to that of let-7b. Conclusions: Our results demonstrated that the decreased expression of let-7b could lead to the high expression of CYP2J2 protein in cancerous tissues. These findings suggest that miRNA let-7b reduces CYP2J2 expression, which may contribute to inhibiting tumor phenotypes. [ABSTRACT FROM AUTHOR]

AbstractFibrosis is the response of heart and other organs to injuries. Excessive fibrosis can cause organ dysfunction or even failure. Transforming-growth factor (TGF)-β is a cytokine that induces fibroblast proliferation and increases the synthesis of a number of extracellular matrix proteins including collagens. Decorin (DCN) is a natural antagonist of TGF-β. In the current study, we investigated the potential antifibrotic effects of DCN gene delivery by a recombinant adeno-associated viral (rAAV) vector to inhibit cardiac fibrosis in old, spontaneously hypertensive rats (SHRs), which develop severe cardiac and kidney fibrosis if without intervention. The rAAV-DCN vector was injected (at a dose of 1 × 1011vector genomes) via the tail vein into 5-month-old male SHRs, resulting in persistent, stable expression of DCN (up to 16 weeks). rAAV-DCN treatment significantly reduced collagen content and fibrosis in the heart and attenuated cardiomyocyte hypertrophy. Hemodynamics data at 16 weeks showed that DCN gene delivery induced a significant increase in left ventricular end-systolic pressure and maximal–minimal rate of pressure increase (±dp/dtmax), but a decrease in left ventricular end-diastolic pressure (p< 0.05), compared with those of control animals. The expression of TGF-β and α-smooth muscle actin, and the phosphorylation levels of Smad2 and p38 MAPK, were markedly reduced by rAAV-DCN treatment as compared with the controls. Thus, these results suggest that rAAV-mediated DCN overexpression led to the inhibition of hypertension-induced cardiac fibrosis and hypertrophy and improved cardiac function, and therefore may have therapeutic potential for organ fibrosis. [ABSTRACT FROM AUTHOR]