Cardiac fibrosis is a primary phenotype of cardiac remodeling that contributes to cardiac dysfunction and heart failure. The expansion and activation of CD4 + T cells in the heart has been identified to facilitate pathological cardiac remodeling and dysfunction; however, the underlying mechanisms remained not well clarified. Herein, we found that exosomes derived from activated CD4 + T cells (CD4-activated Exos) evoked pro-fibrotic effects of cardiac fibroblasts, and their delivery into the heart aggravated cardiac fibrosis and dysfunction post-infarction. Mechanistically, miR-142-3p that was enriched in CD4-activated Exos recapitulated the pro-fibrotic effects of CD4-activated Exos in cardiac fibroblasts, and vice versa. Furthermore, miR-142-3p directly targeted and inhibited the expression of Adenomatous Polyposis Coli (APC), a negative WNT signaling pathway regulator, contributing to the activation of WNT signaling pathway and cardiac fibroblast activation. Thus, CD4-activated Exos promote post-ischemic cardiac fibrosis through exosomal miR-142-3p-WNT signaling cascade-mediated activation of myofibroblasts. Targeting miR-142-3p in CD4-activated Exos may hold promise for treating cardiac remodeling post-MI.
Atrial fibrosis serves as an important contributor to atrial fibrillation (AF). Recent data have suggested that microRNA‐30c (miR‐30c) is involved in fibrotic remodelling and cancer development, but the specific role of miR‐30c in atrial fibrosis remains unclear. The purpose of this study was to investigate the role of miR‐30c in atrial fibrosis and its underlying mechanisms through in vivo and in vitro experiments. Our results indicate that miR‐30c is significantly down‐regulated in the rat abdominal aortic constriction (AAC) model and in the cellular model of fibrosis induced by transforming growth factor‐β1 (TGF‐β1). Overexpression of miR‐30c in cardiac fibroblasts (CFs) markedly inhibits CF proliferation, differentiation, migration and collagen production, whereas decrease in miR‐30c leads to the opposite results. Moreover, we identified TGFβRII as a target of miR‐30c. Finally, transferring adeno‐associated virus 9 (AAV9)‐miR‐30c into the inferior vena cava of rats attenuated fibrosis in the left atrium following AAC. These data indicate that miR‐30c attenuates atrial fibrosis via inhibition of CF proliferation, differentiation, migration and collagen production by targeting TGFβRII, suggesting that miR‐30c might be a novel potential therapeutic target for preventing atrial fibrosis.
Background:
Premature ventricular complex (PVC) with narrow QRS duration originating from proximal left anterior fascicle (LAF) is challenging for ablation. This study was performed to evaluate the safety and feasibility of ablation from right coronary cusp (RCC) for proximal LAF-PVC and to investigate this PVC’s characteristics.
Methods:
Mapping at RCC and left ventricle and ECG analysis were performed in 20 patients with LAF-PVC.
Results:
The earliest activation site (EAS), with Purkinje potential during both PVC and sinus rhythm, was localized at proximal LAF in 8 patients (proximal group) and at nonproximal LAF in 12 patients (nonproximal group). The Purkinje potential preceding PVC-QRS at the EAS in proximal group (32.6±2.5 ms) was significantly earlier than that in nonproximal group (28.3±4.5 ms,
P
=0.025). Similar difference in the Purkinje potentials preceding sinus rhythm QRS at the EAS was also observed between proximal and nonproximal groups (35.1±4.7 versus 25.2±5.0 ms,
P
<0.001). In proximal group, the distance between the EAS to left His bundle and to RCC was shorter than that of nonproximal group (12.3±2.8 versus 19.7±5.0 mm,
P
=0.002, and 3.9±0.8 versus 15.7±7.8 mm,
P
<0.001, respectively). No difference in the distance from RCC to proximal LAF was identified between the 2 groups. PVCs were successfully eliminated from RCC for all proximal groups but at left ventricular EAS for nonproximal groups. The radiofrequency application times, ablation time, and procedure time of nonproximal group were longer than that of proximal group. Electrocardiographic analysis showed that, when compared with nonproximal group, the PVCs of proximal group had narrower QRS duration; smaller S wave in leads I, V
5
, and V
6
; lower R wave in leads I, aVR, aVL, V
1
, V
2
, and V
4
; and smaller q wave in leads III and aVF. The QRS duration difference (PVC-QRS and sinus rhythm QRS) <15 ms predicted the proximal LAF origin with high sensitivity and specificity.
Conclusions:
PVCs originating from proximal LAF, with unique electrocardiographic characteristics, could be eliminated safely from RCC.
Aim: To evaluate the clinical safety and efficacy of radiofrequency catheter ablation for atrial fibrillation (AF) in patients aged ≥80 years. Methods: A total of 333 AF patients aged ≥60 years were enrolled, who underwent contact forceguided radiofrequency catheter ablation with uninterrupted anticoagulation. All patients were followed-up for at least 12 months. Success was defined by the absence of episodes of AF/atrial tachycardia lasting more than 30 seconds after a 3-month blanking period, without antiarrhythmic drugs. Results: Compared to patients aged 60-79 years (Group 2, n = 244), patients aged ≥80 years (Group 1, n = 89) were presented with higher rate of diabetes (36.0% vs 22.1%, P = .011), lower body mass index (23.4 ± 3.1 vs 24.9 ± 3.4 kg/m 2 , P = .001), lower creatinine clearance (56.9 ± 16.5 vs 83.3 ± 24.5 mL/min, P < .001), higher CHA 2 DS 2-VASc score (4.3 ± 1.3 vs 3.3 ± 1.4, P < .001), and HAS-BLED score (2.2 ± 0.8 vs 1.8 ± 0.8, P < .001). Wide antral pulmonary vein isolation was achieved in all patients, and there was no significant difference in procedure time, ablation time, fluoroscopy time, and complications rate between two age groups (P > .05). After a mean followup of 24.4 ± 9.6 months, the overall success rate was 78.2% in Group 1 and 78.9% in Group 2 (P = .622). Conclusions: Radiofrequency ablation with contact force sensing catheters for AF is safe and effective in selected patients aged ≥80 years.
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