Regional Diversities in Fibrogenesis Weighed as a Key Determinant for Atrial Arrhythmogenesis

Figures

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  Figure 1. Atrial fibrosis of left atrium (LA) and right atrium (RA) tissues from healthy and heart failure with reduced ejection fraction (HF) rats. The upper photographs show representative photos with Masson’s trichrome staining of healthy LA and healthy RA atrial fibrosis. The lower photographs show representative photos of HF LA and HF RA atrial fibrosis. Compared to HF RA, HF LA exhibited greater levels of atrial fibrosis. LA and RA from healthy rats revealed a similar extent of atrial fibrosis. HF increased fibrosis to a greater severity in LA than in RA. * p < 0.05 (modified from [36] with permission of the publisher).

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  Figure 2. Membrane gadolinium (Gd3+)-sensitive Ca2+ currents of the left atrium (LA) and right atrium (RA) fibroblasts in healthy and heart failure with reduced ejection fraction (HF) rats. (A). Left and right panels, respectively, reveal tracings of the Gd3+ (100 μmol/L)-sensitive nonselective cation current of LA and RA fibroblasts isolated from healthy rats. Healthy LA fibroblasts exhibited greater Gd3+-sensitive Ca2+ currents compared with healthy RA fibroblasts. (B). Left and right panels, respectively, reveal tracings of the Gd3+ (100 μmol/L)-sensitive nonselective cation current of LA and RA fibroblasts isolated from HF rats. The statistical results revealed that healthy LA fibroblasts exhibited greater Gd3+-sensitive Ca2+ currents compared with healthy RA fibroblasts. HF LA fibroblasts exhibited greater Gd3+-sensitive Ca2+ currents compared with HF RA fibroblasts. LA fibroblasts from HF rats showed higher Gd3+-sensitive currents compared with LA fibroblasts from healthy rats. The insets in the current traces showed the various clamp protocols. * Healthy LA versus healthy RA fibroblasts; $ HF LA versus healthy LA fibroblasts; # HF LA versus HF RA fibroblasts (adapted from the…

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  Figure 3. Illustration of the proposed mechanism that contributes to differential atrial fibrogenesis-induced arrhythmogenesis between the LA and RA. Diverse gene or protein expression induces differential atrial fibrogenesis by modifying nitric oxide, Ca2+, transforming growth factor (TGF)- β, and oxidative stress signaling, thereby activating diversity in atrial arrhythmogenesis through the abnormal distribution of fibrotic tissue, modulations of electrical coupling, paracrine interactions, and biomechanical–electrical interactions. ERα: estrogen receptor-α, eNOS: endothelial nitric oxide synthase, sGC: soluble guanylyl cyclase, ANP: atrial natriuretic peptide, Smad6: SMA and MAD-related protein 6, BMP-10: bone morphogenetic protein-10, HSP-70: heat shock protein-70, Mir: micro RNA, CGRP: calcitonin gene-related peptide, ATF3: activating transcription factor 3.