OBJECTIVE To assess gene expression in cardiomyocytes isolated from patients with aortic stenosis, hypothesizing that maladaptive remodeling and inflammation-related genes are higher in male vs female patients. PATIENTS AND METHODS In this study, 34 patients with aortic stenosis undergoing aortic valve replacement from March 20, 2016, through May 24, 2017, at the German Heart Centre in Berlin, Germany, were included. Isolated cardiomyocytes from interventricular septum samples were used for gene expression analysis. Clinical and echocardiographic data were collected preoperatively. RESULTS Age, body mass index, systolic and diastolic blood pressure, comorbidities, and medication were similar between the 17 male and 17 female patients. The mean ± SD left ventricular end-diastolic diameter (52±9 vs 45±4 mm; P=.007) and posterior wall thickness (14.2±2.5 vs 12.1±1.6 mm; P=.03) were higher in male vs female patients, while ejection fraction was lower in male patients (49%±14% vs 59%±5%; P=.01). Focusing on structural genes involved in the development of cardiac hypertrophy and remodeling, we found that most were expressed higher in male vs female patients. Our modeling analysis revealed that 2 inflammation-related genes, CCN2 and NFKB1, were negatively related to ejection fraction, with this effect being male specific (P=.03 and P=.02, respectively). CONCLUSION These findings provide novel insight into cardiomyocyte-specific molecular changes related to sex differences in pressure overload and a significant male-specific association between cardiac function and inflammation-related genes. Considering these sex differences may contribute toward a more accurate design of research and the development of more appropriate therapeutic approaches for both male and female patients.

中文翻译：

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左心室压力超负荷的特定性别人类心肌细胞基因调控。

目的评估从主动脉瓣狭窄患者分离的心肌细胞中的基因表达，假设男性和女性患者的适应不良重塑和炎症相关基因较高。患者与方法本研究纳入了2016年3月20日至2017年5月24日在德国柏林的德国心脏中心接受主动脉瓣置换术的34例主动脉瓣狭窄患者。从室间隔样本中分离出的心肌细胞用于基因表达分析。术前收集临床和超声心动图数据。结果年龄，体重指数，收缩压和舒张压，合并症和药物治疗在17例男性和17例女性患者中相似。左室舒张末期平均直径的平均值±SD（52±9 vs 45±4 mm; P = .007）和后壁厚度（14。2±2.5和12.1±1.6毫米; P = .03）在男性患者中高于女性，而射血分数在男性患者中较低（49％±14％对59％±5％； P = .01）。着眼于涉及心脏肥大和重塑发展的结构基因，我们发现大多数在男性和女性患者中表达更高。我们的模型分析表明，有2个与炎症相关的基因CCN2和NFKB1与射血分数呈负相关，这种效应是男性特异性的（分别为P = .03和P = .02）。结论这些发现为与压力超负荷性别差异有关的心肌细胞特异性分子变化以及心脏功能与炎症相关基因之间明显的男性特异性关联提供了新的见解。