Redox Biology of Right-Sided Heart Failure

Figures

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  Figure 1. Proposed right ventricles (RV)-specific GATA4 activation mechanism. (A) Pulmonary hypertension produces reactive oxygen species (ROS) in the RV that in turn promote the carbonylation of annexin A1 protein. Carbonylation elicits the annexin A1 degradation by proteasomes, liberating CBF/NF-Y transcription factor that activates Gata4 gene transcription [12]. (B) In the left ventricle (LV), the low CBF/NF-Y-to-annexin A1 ratio with excess annexin A1 does not allow for the efficient CBF/NF-Y activation.

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  Figure 2. Notable metabolites differentially expressed between the RV and LV. The RV and LV wall tissues were dissected from male Sprague Dawley rats and subjected to metabolomics analysis (n = 10). The analysis of metabolomics data revealed 4 biologically notable molecules including (A) (3R)-3-hydroxy-8′-apocarotenol, (B) coprocholic acid, (C) 1alpha,25-dihydroxy-25,25-diphenyl-26,27-dinorvitamin D3 and (D) neuromedin N that exhibited significant differences in the RV and LV. For each molecule, the experimental m/z values (which represent mass), retention time (RT), fold-change (FC) ratio of RV to LV, p-values, name of the molecule, empirical formula, mass of the molecule and the chemical structures are noted. Bar graphs represent means ± SEM of the intensity values obtained from mass spectra.

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  Figure 3. Neurotensin/neuromedin N expression in the heart of rats with pulmonary arterial hypertension (PAH). Male Sprague Dawley rats were subcutaneously injected with SU5416 (20 mg/kg body weight), maintained in hypoxia in a chamber set to maintain 10% O2 [12,26] for three weeks and then in normoxia for 17 weeks [27,28]. Heart tissues were immersed in buffered 10% formalin, embedded in paraffin, cut and mounted on glass slides. Tissue sections were subjected to immunohistochemistry using the neurotensin/neuromedin N (NTS) antibody (catalog # MBS8505326; MyBioSource, Inc., San Diego, CA, USA). (A) Representative immunohistochemistry images of the RVs from 3 pairs of control and PAH animals. (B) The bar graph represents means ± SEM of % NTS antibody-negative cells in the LV and RV. * denotes values significantly different from each other at p < 0.001.