Atrial fibrillation is associated with atrial remodeling, in which connexin 43 (Cx43) and cell hypertrophy play important roles. In this study, apelin-13, an aliphatic peptide, was used to explore the protective effects of the adenosine monophosphate-activated protein kinase (AMPK)/mTOR signaling pathway on Cx43 expression and autophagy, using murine atrial HL-1 cells. The expression of Cx43, AMPK, B-type natriuretic peptide (BNP) and pathway-related proteins was detected by Western blot analysis. Cellular fluorescence imaging was used to visualize Cx43 distribution and the cytoskeleton. Our results showed that the Cx43 expression was significantly decreased in HL-1 cells treated with angiotensin II but increased in cells additionally treated with apelin-13. Meanwhile, apelin-13 decreased BNP expression and increased AMPK expression. However, the expression of Cx43 and LC3 increased by apelin-13 was inhibited by treatment with compound C, an AMPK inhibitor. In addition, rapamycin, an mTOR inhibitor, promoted the development of autophagy, further inhibited the protective effect on Cx43 expression and increased cell hypertrophy. Thus, apelin-13 enhances Cx43 expression and autophagy via the AMPK/mTOR signaling pathway, and serving as a potential therapeutic target for atrial fibrillation., Yifan Chen, Xi Qiao, Lijun Zhang, Xuewen Li, Qinghua Liu., and Obsahuje bibliografii
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia associated with a two-fold increase in mortality caused by a higher risk of stroke and heart failure. Currently, AF is present in ~ 2 % of the general population, and its incidence and prevalence are increasing. Obesity, hypertension, diabetes mellitus, obstructive sleep apnea, and alcohol consumption increase the risk of AF. Each unit of increase in BMI increases the risk of AF by 3 %, and intensive weight loss is also associated with reduced AF recurrence. Hypertension increases the risk of AF by 50 % in men and by 40 % in women, and explains ≈ 20 % of new AF cases. Patients with obstructive sleep apnea are at four times higher risk of developing AF than subjects without sleep apnea. Higher concentrations of pro-inflammatory cytokines, higher amounts of epicardial adipose tissue, and a higher degree of ventricular diffuse myocardial fibrosis are present in AF patients and patients with the aforementioned metabolic disorders. Several prospective cohort studies and randomized trials have been initiated to show whether weight loss and treatment of other risk factors will be associated with a reduction in AF recurrences.
The impact of atrial fibrillation and atrial tachycardias (AF/AT), and their optimal treatment strategy in PH patients is still being discussed. The goal of this study was to evaluate the effect of AF/AT termination on the hemodynamic parameters in PH patients. We compared patients with pre-capillary pulmonary hypertension (PH group), left ventricular heart failure (LV-HF group), and a Control group. A repeated right heart catheterization was performed during the catheter ablation (CA) procedure. The first measurement was done in arrhythmia, the second after the sinus rhythm (SR) was restored. High frequency atrial stimulation was used to simulate AT in patients without arrhythmia presence at the time of the CA. The variation of pressure parameters in PH patients did not differ significantly from the Controls. There was a significant increase in the right ventricle pressure after the SR restoration in the LV-HF group compared to the Controls and PH group (+4 vs. -2 vs. -3 mmHg, p<0.05). The cardiac index (CI) variation was not significant when compared between the study groups. An increase of the CI after the SR restoration was found in those patients with AF (+0.31 l/min/m² [IQR 0.18; 0.58]) in contrast to those patients with organized AT/high frequency atrial stimulation (-0.09 l/min/m², [IQR - 0.45; 0.19]). This difference was statistically significant (p<0.05). The acute hemodynamic response to arrhythmia termination was not significantly different in the PH patients when compared to the Controls. In contrast to AT/high frequency stimulation, the restoration of SR in AF patients leads to an increased CI, irrespective of the presence or absence of PH.
Atrial fibrillation and atrial tachycardias (AF/AT) have been reported as a common condition in patients with pulmonary hypertension (PH). As yet, limited data exists about the significance of the borderline post-capillary pressure component on the occurrence of AF / AT in patients with isolated pre-capillary PH. We retrospectively studied the prevalence of AF / AT in 333 patients (mean age 61±15 years, 44 % males) with pre-capillary idiopathic / familiar pulmonary arterial hypertension, and inoperable chronic thromboembolic pulmonary hypertension. The prevalence of AF / AT was analyzed in different categories of pulmonary artery wedge pressure (PAWP). In the study population overall, the mean PAWP was 10.5±3 mmHg, median of 11 mmHg, range 2-15 mmHg. AF / AT was diagnosed in 79 patients (24 %). The proportion of AF / AT among patients with PAWP below the median (≤11 mmHg) was lower than in subjects with PAWP between 12 and 15 mmHg, 30 (16 %) vs. 46 (35 %), p=0.0001. Compared to the patients with PAWP≤11 mmHg, subjects with PAWP between 12 and 15 mmHg were older (65±13 years vs. 58±16), with more prevalent arterial hypertension [100 (70 %) vs. 106 (55 %)] and diabetes mellitus [50 (35 %) vs. 48 (25 %)], showed larger size of the left atrium (42±7 vs. 40±6 mm), and higher values of right atrium pressure (12±5 vs. 8±5 mmHg), p<0.05 in all comparisons. The prevalence of AF / AT in the group studied increased with the growing post-capillary component.