Chen Shaojie, Wu Nan, Zhang Yike, Lin Zhiqiao, Chen Jiuzhou, Qin Huiyuan, Chen Hongwu, Cui Chang, Yang Gang, Chen Minglong
Division of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing China.
Division of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing China.
Heart Rhythm. 2025 Jul;22(7):e172-e182. doi: 10.1016/j.hrthm.2024.09.022. Epub 2024 Sep 14.
Postmenopausal women with atrial fibrillation (AF) exhibit a higher level of atrial fibrosis and a higher recurrence rate after ablation compared with men. However, the underlying mechanism remains unclear.
The purpost of this study was to investigate the mechanism through which menopause promotes atrial fibrosis.
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. Follicle-stimulating hormone (FSH) stimulation was applied in male mice for 3 months. OVX was also applied in an angiotensin II (Ang II)-induced pressure overload mouse model, after programmed electrical stimulation and structural analyses. Bulk RNA sequencing (RNA-seq) was performed to elucidate potential mechanisms.
Women demonstrated a significantly higher LVA burden than men (P < .001). A positive correlation was observed between LVA burden and FSH level (P = .002). Mice in the OVX group exhibited a significantly higher incidence of AF (P = .040) and atrial fibrosis (P = .021) compared with the Sham group, which could be attenuated by adeno-associated virus encoding small interfering RNA against Fshr. In male CREM-IbΔC-X mice, FSH stimulation promoted the occurrence of AF (P = .035) and atrial fibrosis (P = .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.
Postmenopausal women exhibited a higher LVA burden than men, which was positively correlated with FSH level. FSH promoted atrial fibrosis through oxidative stress.
与男性相比，绝经后房颤（AF）女性表现出更高水平的心房纤维化和消融术后更高的复发率。然而，潜在机制仍不清楚。
本研究的目的是探讨绝经促进心房纤维化的机制。
在一个AF女性前瞻性队列中，进行回归分析以评估低电压区（LVA）与性激素水平之间的关系。对CREM-IbΔC-X小鼠（一种自发性AF模型）进行双侧卵巢切除术（OVX）。进行心电图、超声心动图和Masson染色。对雄性小鼠应用促卵泡激素（FSH）刺激3个月。在程序电刺激和结构分析后，也对血管紧张素II（Ang II）诱导的压力超负荷小鼠模型进行OVX。进行批量RNA测序（RNA-seq）以阐明潜在机制。
女性的LVA负担明显高于男性（P <.001）。观察到LVA负担与FSH水平之间呈正相关（P =.002）。与假手术组相比，OVX组小鼠的AF发生率（P =.040）和心房纤维化发生率（P =.021）明显更高，这可通过编码针对Fshr的小干扰RNA的腺相关病毒来减轻。在雄性CREM-IbΔC-X小鼠中，FSH刺激促进了AF的发生（P =.035）和心房纤维化（P =.002）。在Ang II诱导的雌性小鼠中，OVX促使心房纤维化，增加AF诱导性，并缩短心房有效不应期，这可通过敲低Fshr来减轻。RNA-seq表明线粒体功能障碍。
绝经后女性的LVA负担高于男性，且与FSH水平呈正相关。FSH通过氧化应激促进心房纤维化。
