Effects of chronic atrial fibrillation on gap junction distribution in human and rat atria

Polontchouk, Lioudmila; Haefliger, Jacques‐Antoine; Ebelt, Berit; Schaefer, Thomas; Stuhlmann, Dominik; Mehlhorn, Uwe; Kuhn‐Régnier, Ferdinand; Vivie, E. R. de; Dhein, Stefan

doi:10.1016/s0735-1097(01)01443-7

Cited by 265 publications

(216 citation statements)

References 35 publications

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“…We found that the AAC‐induced upregulation of Cx43 proteins was more prone to redistribute to the lateral side of the cells. When the normal side‐to‐side gap junctions are redistributed at the lateral margins, the effective transverse propagation of conduction velocity decreases 43. Together with a reduction in the amount of Cx40 and a specific reduced Cx40/Cx43 ratio, these results contributed to localized conduction abnormalities, thus facilitating the self‐perpetuation of reentry pathways in AF 40.…”

Section: Discussionmentioning

confidence: 99%

Activin Receptor‐Like Kinase 4 Haplodeficiency Mitigates Arrhythmogenic Atrial Remodeling and Vulnerability to Atrial Fibrillation in Cardiac Pathological Hypertrophy

Wang

Chen

Zhang

et al. 2018

JAHA

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BackgroundActivin receptor‐like kinase 4 (ALK4) is highly expressed in mammal heart. Atrial fibrillation (AF) is closely related to ventricular pressure overload. Because pressure overload increases atrial pressure and leads to atrial remodeling, it would be informative to know whether ALK4 exerts potential effects on atrial remodeling and AF vulnerability in a pressure‐overload model.Methods and ResultsWild‐type littermates and ALK4+/− mice were subjected to abdominal aortic constriction or a sham operation. After 4 or 8 weeks, echocardiographic and hemodynamic measurements were performed, and inducibility of AF was tested. The hearts were divided into atria and ventricles and then were fixed in formalin for staining, or they were weighted and snap‐frozen for quantitative real‐time polymerase chain reaction and Western blot analysis. Compared with wild‐type littermates, ALK4+/− mice demonstrated a similar extent of atrial hypertrophy but significantly suppressed atrial fibrosis at 8 weeks post–abdominal aortic constriction. ALK4 haplodeficiency partially blocked abdominal aortic constriction–induced upregulation of monocyte chemotactic protein 1 and interleukin‐6, and the increased chemotaxin of macrophages. ALK4 haplodeficiency also blunted a reduction of connexin 40 and redistribution of connexin 43 from the intercalated disk to the lateral membranes, thereby improving localized conduction abnormalities. Meanwhile, ALK4 haplodeficiency inhibited abdominal aortic constriction–induced decreased IN a, IC a‐L and IK 1 densities as well as the accompanying action potential duration shortening. Mechanistically, ALK4 haploinsufficiency resulted in the suppression of Smad2/3 activity in this model.ConclusionsOur results demonstrate that ALK4 haplodeficiency ameliorates atrial remodeling and vulnerability to AF in a pressure‐overload model through inactivation of the Smad2/3 pathway, suggesting that ALK4 might be a potential therapeutic target in combating pressure overload–induced AF.

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Section: Discussionmentioning

confidence: 99%

Activin Receptor‐Like Kinase 4 Haplodeficiency Mitigates Arrhythmogenic Atrial Remodeling and Vulnerability to Atrial Fibrillation in Cardiac Pathological Hypertrophy

Wang

Chen

Zhang

et al. 2018

JAHA

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“…mechanism of insulin resistance that results in impaired atrial synchronicity and atrial electrical remodeling is still not well understood. It may be related to an altered myocardial protein degradation, 30 atrial myocardial fibrosis 31 or disruption of cardiocyte coupling at gap junctions, 32 which may finally cause electrophysiological instability in the atrial myocardium and lead to impaired atrial synchronicity and atrial electrical remodeling. Further studies are needed to identify in detail the exact mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Impaired atrial synchronicity in patients with metabolic syndrome associated with insulin resistance and independent of hypertension

Yang

Gong

et al. 2009

Hypertens Res

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The risk of developing atrial fibrillation is increased in patients with metabolic syndrome, but atrial conduction properties are uncharacterized in patients who have metabolic syndrome without atrial arrhythmia. We used tissue Doppler imaging to evaluate intra-and interatrial synchronicity in such patients. The imaging was performed in 145 patients with metabolic syndrome and 110 controls. Atrial synchronicity was determined from the intervals between the onset of the P-wave to the onset of the A-wave at the left atrial free wall (P-LA), interatrial septum (P-IAS) and right atrial free wall (P-RA). Intra-atrial synchronicity was defined as the differences between P-IAS and P-RA (RA synchronicity) and between P-LA and P-IAS (LA synchronicity). Interatrial synchronicity was defined as the difference between P-LA and P-RA. P-LA and P-IAS were significantly prolonged in the metabolic syndrome group relative to the control group (P-LA: 64.34 ± 13.99 vs. 55.35 ± 12.67, Po0.001; P-IAS: 36.49±12.39 vs. 31.55±11.61, P¼0.001), whereas P-RA showed no difference. As a result, this caused impaired intra-and interatrial synchronicity in patients with metabolic syndrome. Stepwise multivariate linear analysis revealed insulin resistance as an independent predictor of impaired intra-and interatrial synchronicity. Subgroup analysis indicated that there was no difference in atrial asynchrony between non-hypertensive and hypertensive subgroups in metabolic syndrome patients. In conclusion, patients with metabolic syndrome without atrial arrhythmia have impaired intra-and interatrial synchronicity. Insulin resistance has an important role in impaired atrial conduction in these patients.

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“…The varying results regarding CV changes in ATR substrate may point to the existence of multiple factors and changes that can affect CV. A decreased I Na would tend to decrease CV 124 , while a decreased ERP or an increased connexin expression 75,125,126 would have the opposite effect.…”

Section: Electrophysiological Properties Of Vs and Atr Substratementioning

confidence: 98%

“…Our results are in accordance with Fareh et al 27 and Wijfells et al 74 , where pacing techniques similar to ours (from left and right atrial appendage) were used for the calculation. Furthermore, animal and human studies 125,126 showed an increased connexin (Cx40) expression especially in the lateral cell membrane, potentially contributing to anisotropic impulse conduction, while other studies 127,128 found Cx40 significantly reduced in patients with persistent AF.…”

Section: Electrophysiological Properties Of Vs and Atr Substratementioning

confidence: 99%

Differences in atrial fibrillation properties under vagal nerve stimulation versus atrial tachycardia remodeling

et al. 2009

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Effects of chronic atrial fibrillation on gap junction distribution in human and rat atria

Abstract: This experimental study showed that AF is accompanied by spatial remodeling of gap junctions that might induce changes in the biophysical properties of the tissue.

Cited by 265 publications

References 35 publications

Activin Receptor‐Like Kinase 4 Haplodeficiency Mitigates Arrhythmogenic Atrial Remodeling and Vulnerability to Atrial Fibrillation in Cardiac Pathological Hypertrophy

Activin Receptor‐Like Kinase 4 Haplodeficiency Mitigates Arrhythmogenic Atrial Remodeling and Vulnerability to Atrial Fibrillation in Cardiac Pathological Hypertrophy

Impaired atrial synchronicity in patients with metabolic syndrome associated with insulin resistance and independent of hypertension

Differences in atrial fibrillation properties under vagal nerve stimulation versus atrial tachycardia remodeling

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