During chronic hepatitis B virus (HBV) infection

We analyzed the effect of conditional, ␣MHC-dependent genetic ␤-catenin depletion and stabilization on cardiac remodeling following experimental infarct. ␤-Catenin depletion significantly improved 4-week survival and left ventricular (LV) function (fractional shortening: CT ⌬ex3-6 : 24 ؎ 1.9%; ␤-cat ⌬ex3-6 : 30.2 ؎ 1.6%, P < 0.001). ␤-Catenin stabilization had opposite effects. No significant changes in adult cardiomyocyte survival or hypertrophy were observed in either transgenic line. Associated with the functional improvement, LV scar cellularity was altered: ␤-catenin-depleted mice showed a marked subendocardial and subepicardial layer of small cTnT pos cardiomyocytes associated with increased expression of cardiac lineage markers Tbx5 and GATA4. Using a Cre-dependent lacZ reporter gene, we identified a noncardiomyocyte cell population affected by ␣MHC-driven gene recombination localized to these tissue compartments at baseline. These cells were found to be cardiac progenitor cells since they coexpressed markers of proliferation (Ki67) and the cardiomyocyte lineage (␣MHC, GATA4, Tbx5) but not cardiac Troponin T (cTnT). The cell population overlaps in part with both the previously described c-kit pos and stem cell antigen-1 (Sca-1) pos precursor cell population but not with the Islet-1 pos precursor cell pool. An in vitro coculture assay of highly enriched (>95%) Sca-1 pos cardiac precursor cells from ␤-catenin-depleted mice compared to cells isolated from control littermate demonstrated increased differentiation toward ␣-actin pos and cTnT pos cardiomyocytes after 10 days (CT ⌬ex3-6 : 38.0 ؎ 1.0% ␣-actin pos ; ␤-cat ⌬ex3-6 : 49.9 ؎ 2.4% ␣-actin pos , P < 0.001). We conclude that ␤-catenin depletion attenuates postinfarct LV remodeling in part through increased differentiation of GATA4 pos /Sca-1 pos resident cardiac progenitor cells. D espite adaptive mechanisms including activation of cardiomyocyte survival pathways and hypertrophy, left ventricular (LV) remodeling often progresses to cardiac dilation and heart failure (1). Recently, the quantitative contribution of endogenous cardiac regeneration was found to account for at least 25% of cardiomyocytes in the infarct border zone (2). However, essential characteristics of this cardiac precursor cell pool, like signaling pathways directing differentiation and/or proliferation, are largely unknown.Transcription factors essential for embryonic cardiac development also affect adult cardiac remodeling in mice (3). Regulation of the Wnt/␤-catenin pathway differentially regulates embryonic cardiac progenitor cells prespecification, renewal, and differentiation in the cardiac mesoderm (4-7). Activation of the Wnt/␤-catenin pathway specifically stimulates Islet-1 cardiac progenitor cells proliferation while delaying differentiation. Conversely, increased expression of Wnt signaling inhibitors in ␣MHC pos cardiac precursor cells isolated from embryoid bodies lead to increased cardiomyocyte differentiation (8).We previously reported that downregulation of ␤-catenin in ...

Abstract-The armadillo-related protein ␤-catenin has multiple functions in cardiac tissue homeostasis: stabilization of ␤-catenin has been implicated in adult cardiac hypertrophy, and downregulation initiates heart formation in embryogenesis. The protein is also part of the cadherin/catenin complex at the cell membrane, where depletion might result in disturbed cell-cell interaction similar to N-cadherin knockout models. Here, we analyzed the in vivo role of ␤-catenin in adult cardiac hypertrophy initiated by angiotensin II (Ang II). The cardiac-specific mifepristone-inducible ␣MHC-CrePR1 transgene was used to induce ␤-catenin depletion (loxP-flanked exons 3 to 6, ␤-cat ⌬ex3-6 mice) or stabilization (loxP-flanked exon 3, ␤-cat ⌬ex3 mice). Levels of ␤-catenin were altered both in membrane and nuclear extracts. Analysis of the ␤-catenin target genes Axin2 and Tcf-4 confirmed increased ␤-catenin-dependent transcription in ␤-catenin stabilized mice. In both models, transgenic mice were viable and healthy at age 6 months. ␤-Catenin appeared dispensable for cell membrane function. Ang II infusion induced cardiac hypertrophy both in wild-type mice and in mice with ␤-catenin depletion. In contrast, mice with stabilized ␤-catenin had decreased cross-sectional area at baseline and an abrogated hypertrophic response to Ang II infusion. Stabilizing ␤-catenin led to impaired fractional shortening compared with control littermates after Ang II stimulation. This functional deterioration was associated with altered expression of the T-box proteins Tbx5 and Tbx20 at baseline and after Ang II stimulation. In addition, atrophy-related protein IGFBP5 was upregulated in ␤-catenin-stabilized mice. These data suggest that ␤-catenin downregulation is required for adaptive cardiac hypertrophy. (Circ Res.

Hand disinfection is an important measure to prevent transmission of norovirus (formerly called Norwalk-like viruses) from hands or environmental surfaces to other objects. Therefore, three types of alcohol (ethanol, 1-and 2-propanol) were examined for their virus-inactivating properties against feline calicivirus (FCV) as a surrogate for norovirus. Tests were performed as quantitative suspension assays or as in vivo experiments with artificially contaminated fingertips. The in vitro experiments showed that 1-propanol was more effective than ethanol and 2-propanol for the inactivation of FCV: in tests with the 50 and 70% solutions of the different alcohols, a 10 4 -fold reduction was observed with 1-propanol after 30 s, whereas the other alcohols were effective only after 3 min contact time. The greatest efficacy did not occur at the highest concentrations (80%). The following concentrations (extrapolated data) showed the greatest virusinactivating properties in the suspension test: ethanol 67%, 2-propanol 58% (exposure times of 1 min) and 1-propanol 60% (exposure time of 30 s). The results from fingertips experiments with 70 and 90% solutions and an application time of 30 s confirmed these findings: the 70% alcoholic solutions were more effective than the 90% solutions. In contrast to the suspension tests, 70% ethanol showed the greatest efficacy in vivo with a log 10 reduction factor (RF) of 3.78 compared with 70% 1-propanol (RF 3.58), 70% 2-propanol (RF 2.15) and hard water (RF 1.23). Ethanol and 1-propanol-based solutions with a high alcohol content thus appear most effective.