Shaojie Chen, Nan Wu, Yike Zhang, Zhiqiao Lin, Jiuzhou Chen, Huiyuan Qin, Hongwu Chen, Chang Cui, Gang Yang, Minglong Chen
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引用次数: 0
Abstract
Background: Postmenopausal women with atrial fibrillation (AF) exhibit a higher level of atrial fibrosis and a higher recurrence rate after ablation compared to men. However, the underlying mechanism remains unclear.
Objective: To investigate the mechanism through which menopause promotes atrial fibrosis.
Methods: In a prospective cohort of women with AF, regression analyses were conducted to assess the relationship between low-voltage area (LVA) and sex hormone levels. CREM-IbΔC-X mice, a spontaneous AF model, underwent bilateral ovariectomy (OVX). Electrocardiograms, echocardiograms, and Masson staining were performed. FSH stimulation was applied in male mice for three months. OVX was also applied in an angiotensin II (Ang II) induced pressure overload mouse model, following programmed electrical stimulation and structural analyses. Bulk RNA sequencing (RNA-seq) was performed to elucidate potential mechanisms.
Results: Women demonstrated a significantly higher LVA burden than men (P<0.001). A positive correlation was observed between LVA burden and FSH level (P=0.002). Mice in the OVX group exhibited a significantly higher incidence of AF (P=0.040) and atrial fibrosis (P=0.021) compared to the Sham group, which could be attenuated by AAV-siFshr. In male CREM-IbΔC-X mice, FSH stimulation promoted the occurrence of AF (P=0.035) and atrial fibrosis (P=0.002). In Ang II-induced female mice, OVX prompted atrial fibrosis, increased AF inducibility, and shortened atrial effective refractory period, which could be attenuated with knockdown of Fshr. RNA-seq indicated mitochondrial dysfunction.
Conclusion: Postmenopausal women exhibited a higher LVA burden than men, which was positively correlated with FSH level. FSH promoted atrial fibrosis through oxidative stress.
期刊介绍:
HeartRhythm, the official Journal of the Heart Rhythm Society and the Cardiac Electrophysiology Society, is a unique journal for fundamental discovery and clinical applicability.
HeartRhythm integrates the entire cardiac electrophysiology (EP) community from basic and clinical academic researchers, private practitioners, engineers, allied professionals, industry, and trainees, all of whom are vital and interdependent members of our EP community.
The Heart Rhythm Society is the international leader in science, education, and advocacy for cardiac arrhythmia professionals and patients, and the primary information resource on heart rhythm disorders. Its mission is to improve the care of patients by promoting research, education, and optimal health care policies and standards.