Integrated Regional Cardiac Hemodynamic Imaging and RNA Sequencing Reveal Corresponding Heterogeneity of Ventricular Wall Shear Stress and Endocardial Transcriptome.

BACKGROUND: Unlike arteries, in which regionally distinct hemodynamics are associated with phenotypic heterogeneity, the relationships between endocardial endothelial cell phenotype and intraventricular flow remain largely unexplored. We investigated regional differences in left ventricular wall shear stress and their association with endocardial endothelial cell gene expression. METHODS AND RESULTS: Local wall shear stress was calculated from 4-dimensional flow magnetic resonance imaging in 3 distinct regions of human (n=8) and pig (n=5) left ventricle: base, adjacent to the outflow tract; midventricle; and apex. In both species, wall shear stress values were significantly lower in the apex and midventricle relative to the base; oscillatory shear index was elevated in the apex. RNA sequencing of the endocardial endothelial cell transcriptome in pig left ventricle (n=8) at a false discovery rate ≤10% identified 1051 genes differentially expressed between the base and the apex and 327 between the base and the midventricle; no differentially expressed genes were detected at this false discovery rate between the apex and the midventricle. Enrichment analyses identified apical upregulation of genes associated with translation initiation including mammalian target of rapamycin, and eukaryotic initiation factor 2 signaling. Genes of mitochondrial dysfunction and oxidative phosphorylation were also consistently upregulated in the left ventricular apex, as were tissue factor pathway inhibitor (mean 50-fold) and prostacyclin synthase (5-fold)-genes prominently associated with antithrombotic protection. CONCLUSIONS: We report the first spatiotemporal measurements of wall shear stress within the left ventricle and linked regional hemodynamics to heterogeneity in ventricular endothelial gene expression, most notably to translation initiation and anticoagulation properties in the left ventricular apex, in which oscillatory shear index is increased and wall shear stress is decreased.

The efficacy of anti-viral therapy on hepatitis B virus-associated glomerulonephritis: A systematic review and meta-analysis.

OBJECTIVES: To assess the efficacy of anti-viral therapy on hepatitis B virus associated glomerulonephritis (HBV-GN). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We searched PubMed, Embase and Cochrane Library for prospective controlled trials which assessed the efficacy of anti-viral therapy on HBV-GN in adult or pediatric patients between January, 1970 and October, 2010. Results were summarized using fixed-effects model because of an absence of heterogeneity among the studies (I(2) = 0%). RESULTS: Six trials with a total of 159 patients were included; among them five trials were specified as hepatitis B virus-associated membranous glomerulonephritis (HBV-MN). In adult patients, the incidence of proteinuria remission, not only total remission (complete remission CR + partial remission PR) (2.97 to 109.93, P = 0.002) but also CR (1.18 to 16.11, P = 0.03), significantly increased in the anti-viral treatment. In pediatric patients, only the incidence of total remission (1.77 to 17.75, P = 0.003) was increased significantly; the incidence of CR was not pooled with clinical and statistical heterogeneity (I(2) = 81.5%, P = 0.004).Combine the data from adult and pediatric patients with HBV-MN, the same results were found. All the results of proteinuria remission kept with virologic response (VR), including HBeAg conversion (5.68 to 40.04, P < 0.00001) and reduction of HBV-DNA (5.60 to 463.16, P = 0.0005). CONCLUSIONS: Antiviral therapy including IFN and lamivudine is effective on remission of proteinuria, HBeAg clearance, and HBV-DNA reduction.