Le Nezet Emma, Tam Rose, Li Zhonglin, Gaudreault Nathalie, Mathieu Patrick, Côté Nancy, Guisle Isabelle, Thériault Sébastien, Bossé Yohan, Clavel Marie-Annick
Institut Universitaire de Cardiologie et Pneumologie de Québec (Quebec Heart & Lung Institute), Université Laval, Québec City, Québec, Canada.
CJC Open. 2025 Feb 17;7(8):1027-1037. doi: 10.1016/j.cjco.2025.02.007. eCollection 2025 Aug.
Valvular lesions in calcific aortic valve stenosis are sex-specific: female patients reach a similar level of severity as male patients but with less valvular calcification and more valvular fibrosis. We thus aim to assess the transcriptome of stenotic aortic valves according to patients' sex.
A total of 300 valves were collected, and genomewide gene expression was quantified using a microarray on 240. Among these, 62 female patients were matched with 62 male patients, for age (within 2 years), body mass index (within 2 kg/m), arterial pressure (within 10/5 mm Hg), diabetes (exact), hypertension (exact), and calcific aortic valve stenosis severity. Among the 60 remaining valves, 16 female and 16 male patients were similarly matched for real-time quantitative polymerase chain reaction analysis.
Clinical and echocardiographic characteristics of the patients were comparable between female and male patients, except for the incidence of coronary artery disease and body surface area (greater in male patients). A total of 190 genes were regulated differently in female vs male patients-132 on autosomes, and 58 on sexual chromosomes. Differences were found in inflammation and lipid metabolism-associated genes. Genes linked to intensified fibrosis processes (eg, , , ) were overexpressed in female vs male patients. Genes associated with increased calcification were overexpressed in both male () and female () patients. Genes involved in apoptosis (, , ) were overexpressed in female vs male patients. Only was validated by real-time quantitative polymerase chain reaction analyses.
This study provides evidence that sex may influence aortic valve gene expression through different mechanisms in female vs male individuals.
钙化性主动脉瓣狭窄中的瓣膜病变存在性别差异：女性患者达到与男性患者相似的严重程度，但瓣膜钙化较少，纤维化较多。因此，我们旨在根据患者性别评估狭窄主动脉瓣的转录组。
共收集了300个瓣膜，其中240个使用微阵列进行全基因组基因表达定量。在这些样本中，62名女性患者与62名男性患者在年龄（2年内）、体重指数（2kg/m²内）、动脉压（10/5mmHg内）、糖尿病（确切）、高血压（确切）和钙化性主动脉瓣狭窄严重程度方面进行了匹配。在其余60个瓣膜中，16名女性患者和16名男性患者在实时定量聚合酶链反应分析中进行了类似匹配。
除冠心病发病率和体表面积（男性患者更大）外，女性和男性患者的临床和超声心动图特征具有可比性。女性与男性患者共有190个基因的调控存在差异——132个在常染色体上，58个在性染色体上。在炎症和脂质代谢相关基因中发现了差异。与强化纤维化过程相关的基因（如……）在女性患者中比男性患者中表达上调。与钙化增加相关的基因在男性（……）和女性（……）患者中均表达上调。参与细胞凋亡的基因（……）在女性患者中比男性患者中表达上调。只有……通过实时定量聚合酶链反应分析得到验证。
本研究提供了证据表明，性别可能通过不同机制影响女性和男性个体的主动脉瓣基因表达。
