Atrial Fibrillation Promotion in a Rat Model of Rheumatoid Arthritis

Figures

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  Figure 1. CIA‐induced systemic and atrial inflammation. A and B, Serum levels of IL‐6 (interleukin 6) and TNF‐α (tumor necrosis factor α) 8 weeks after primary collagen II and Freund's incomplete adjuvant injection (n=10 per group). C and D, Representative Western blots and quantification of IL‐6 and TNF‐α protein expression in atrial tissues (n=6 per group). E and F, Examples of hematoxylin and eosin staining (n=6 per group). **P<0.01, ***P<0.001, vs the CON group; ### P<0.001, vs baseline. Scale bar=50 μm. Arrow indicates the accumulation of inflammatory cells. CIA indicates collagen‐induced arthritis; CON, control.

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  Figure 2. AF susceptibility and electrophysiological parameters changes. A and B, Examples of AF induction attempts in (A) a control rat and (B) a CIA rat. C, AF inducibility. D, AF duration. E, AERP. F, Intra‐atrium CT. G and H, AF duration was significantly and positively correlated with the serum levels of IL‐6 (interleukin 6; r=0.82, P<0.01) and TNF‐α (tumor necrosis factor α; r=0.84, P<0.01). *P<0.05, **P<0.01, ***P<0.001, vs the CON group, n=10 per group. AERP indicates atrial effective refractory period; AF, atrial fibrillation; CIA, collagen‐induced arthritis; CON, control; CT, conduction time; EGM, electrogram; SR, sinus rhythm.

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  Figure 3. Echocardiographic variables changes. A, Echocardiography images of left atrial (LA) and right atrial (RA) dimensions in the control (CON) and collagen‐induced arthritis (CIA) groups. B through D, LA diameter, RA up–down diameter and RA left–right diameter in CON and CIA rats. E through I, Left ventricular diameter at end diastole (LVDd) and systole (LVDs), left ventricular ejection fraction (LVEF), peak E‐wave velocity, and right ventricular diameter (RVD) in CON and CIA rats. *P<0.05, vs the CON group, n=10 per group.

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  Figure 4. Effect of collagen‐induced arthritis (CIA) on atrial fibrosis. A, Examples of Masson's trichrome staining. B, Collagen volume fraction (CVF) of each group, n=8 per group. C through F, Representative Western blots and quantification of protein expressions of collagen I, collagen III, TGF‐β1 (transforming growth factor‐β1), and α‐SMA (α–smooth muscle actin) in atrial tissues; n=6 per group. **P<0.01, ***P<0.001, vs the control (CON) group. Scale bar=50 μm.

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  Figure 5. CIA increased atrial myocytes apoptosis. A, Examples of TUNEL (terminal deoxynucleotidyl transferase mediated dUTP nick‐end labeling) staining. B, The number of apoptotic cells per field, n=8 per group. C through E, Representative western blots and quantification of protein expressions of Bcl‐2, Bax, and CASP‐3 (caspase 3) in atrial tissues; n=6 per group. **P<0.01, ***P<0.001, vs the CON group. Scale bar=50 μm. CIA indicates collagen‐induced arthritis; CON, control.

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  Figure 6. CIA‐induced autophagy in the atria. A and B, Representative electron microphotographs showing autophagic vacuoles in atrial myocytes. C and D, Representative Western blots and quantification of protein expressions of LC3B and ATG5 in atrial tissues. ***P<0.001, vs the CON group, n=6 per group. Scale bar=2 μm. Arrows indicate the autophagic vacuoles. CIA indicates collagen‐induced arthritis; CON, control.

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  Figure 7. Protein expressions of connexins, Nav1.5, and the main ion channels in the atria. A and B, Representative Western blots and quantification of protein expressions of total Cx40 (connexin 40) (A) and total Cx43 (connexin 43) (B) in control (CON) and collagen‐induced arthritis (CIA) rats. C, Representative Western blots and quantification of protein expressions of Nav1.5 in CON and CIA rats. D through H, Representative Western blots and quantification of protein expressions of Cav 1.2, Kir 2.1, Kir 3.1, Kir 3.4, and Kv 1.5 in atrial tissues of CON and CIA rats. n=6 per group.

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  Figure 8. Atrial sympathetic remodeling induced by collagen‐induced arthritis (CIA). A through D, Atrial immunostaining and mean density of GAP43 (growth associated protein 43)–positive nerves (A and B) and TH (tyrosine hydroxylase)–positive nerves (C and D), n=8 per group. E through G, Representative Western blots and quantification of protein expressions of GAP43, TH, and NGF (nerve growth factor) in atrial tissues; n=6 per group. ***P<0.001, vs the control (CON) group. Scale bar=50 μm. Arrows indicate the GAP43‐ and TH‐positive nerves.