Electrical, structural, and autonomic atrial remodeling underlies atrial fibrillation in inflammatory atrial cardiomyopathy

Figures

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  FIGURE 1. AF vulnerability in inflammatory atrial cardiomyopathy. (A) Representative histology of the atrium on days 0, 14, and 42 after immunization with MyHC-α (scale bars = 50 μm). The right bar graphs indicate the number of infiltrating mononuclear cells and fibrotic areas in the atria. (B) The bar graphs represent echocardiographic parameters at the indicated time-points. (C) The AF induction study was performed at baseline and 14, 28, and 42 days after MyHC-α immunization. Representative surface and endocardial electrocardiograms are shown. AF was induced by atrial burst pacing followed by spontaneous termination to sinus rhythm (SR). AF induction rate (D), AF duration (E), and right atrial ERP at basic cycle lengths of 200 ms (F) and 150 ms (G). The results are presented as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001 using the Kruskal–Wallis test with Dunn’s test. MyHC-α, α-myosin heavy chain; AF, atrial fibrillation; ERP, effective refractory period; SEM, standard error of the mean.

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  FIGURE 2. Inflammatory cell infiltration, cytokine expression, and STAT3 activation in inflammatory atrial cardiomyopathy. (A) Flow cytometric analyses of the cardiac-infiltrating cells in the atria. (B) Expression of inflammation- and fibrosis-related genes in the atria. (C) Semi-quantitative membrane-based cytokine array analysis of the atrium performed on day 14. The bar graph shows the signal intensity of each cytokine when the control was set to 1. (D) Western blot analysis of the atrium. The bar graph shows the densitometric ratio of phosphorylated STAT3 (pSTAT3) to total STAT3. The results are presented as the mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001 using the Mann–Whitney U test, and Kruskal–Wallis test with Dunn’s test. STAT3, signal transducer and activator of transcription 3; SEM, standard error of the mean.

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  FIGURE 3. Electrical remodeling in inflammatory atrial cardiomyopathy. (A) Expression of electrical remodeling-related genes in the atria. (B) Western blot analysis of the atrium. The bar graph shows the ratio of Kir2.1 to β-actin. (C) Immunohistochemical analysis of Cx40 in the atrium. The arrows indicate organized Cx40 complexes at the junctional plaques between two adjacent cardiomyocytes. The arrowheads indicate Cx40 lateralization. Scale bars = 50 μm. The bar graph shows the Cx40 lateralization quantitative analysis results. *P < 0.05, **P < 0.01, ***P < 0.001 using the Kruskal–Wallis test with Dunn’s test. Cx40, anti-connexin 40.

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  FIGURE 4. Autonomic remodeling in inflammatory atrial cardiomyopathy. (A,B) Immunostaining for TH (A) and ChT (B) in the atrium. Nerve areas (indicated by arrows) immunopositive for TH and ChT were determined using ImageJ software. The bar graphs show the relative TH+ or ChT+ nerve area when D0 was set to 1. Scale bars = 50 μm (C) qRT-PCR analysis of autonomic remodeling-related genes. *P < 0.05, **P < 0.01, ***P < 0.001 using the Kruskal–Wallis test with Dunn’s test. TH, anti-tyrosine hydroxylase; ChT, anti-choline transporter; qRT-PCR, quantitative reverse transcription polymerase chain reaction.