Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Bolyai János Research Scholarship - BO/00837/21 to O.A., National Research, Development and Innovation Office (NKFIH) of Hungary - K135076 to B.M. Introduction Regular physical activity results in characteristic structural and functional changes in the heart, which are collectively referred to as the athlete’s heart. However, the extent of exercise-induced left ventricular (LV) hypertrophy and functional changes show significant differences between men and women, the molecular background of which is not fully elucidated. Purpose The aim of this study was to provide a proteomic characterization of long-term, intense exercise-induced LV myocardial hypertrophy in a rat model, with a focus on sex-related differences. Methods Our rats were divided into trained (FEx) and control female (FCo) as well as trained (MEx) and control male (MCo) groups. In the trained groups, athlete’s heart was induced by a 12-week swimming protocol. Myocardial hypertrophy was confirmed by echocardiography and functional adaptation by pressure-volume analysis. Proteomic measurements based on liquid chromatograph-coupled mass spectrometry were performed on proteins isolated from our LV myocardial samples. Results Echocardiography and post-mortem myocardial mass showed significant LV hypertrophy in both sexes, which was more pronounced in female animals (tibial length normalized LV muscle mass: + 17.4% MEx vs. MCo, + 31.0% FEx vs. FCo). LV contractility increased to the same extent in both sexes. Relative expression of 3074 proteins were determined by proteomics. There was a significant change in expression of 229 proteins in males and 599 in females compared to the level of same-sex controls. Based on our gene ontological analysis, physiological LV remodeling in females is characterized by increased expression of proteins in cellular respiration and fatty acid oxidation, whereas in males, proteins that bind to the actin cytoskeleton is primarily increased. Conclusions Our data suggests that physiological LV hypertrophy resulting from regular, balanced exercise is associated with sex-specific changes in the myocardial proteome. Our results contribute to the understanding of the development of physiological myocardial hypertrophy.

中文翻译：

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运动员心脏的性别相关蛋白质组学差异

资金致谢 资金来源类型：公共拨款——仅限国家预算。主要资金来源：Bolyai János 研究奖学金 - BO/00837/21 至 OA，匈牙利国家研究、发展和创新办公室 (NKFIH) - K135076 至 BM ，统称为运动员的心脏。然而，运动引起的左心室 (LV) 肥大和功能变化的程度在男性和女性之间表现出显着差异，其分子背景尚未完全阐明。目的 本研究的目的是提供大鼠模型中长期、剧烈运动诱导的 LV 心肌肥大的蛋白质组学特征，重点是性别相关差异。方法 我们的大鼠分为训练组 (FEx) 和对照雌性 (FCo) 组以及训练组 (MEx) 和对照组雄性 (MCo) 组。在训练组中，运动员的心脏通过 12 周的游泳方案进行诱导。心肌肥大通过超声心动图和压力容积分析的功能适应得到证实。对从我们的 LV 心肌样本中分离的蛋白质进行基于液相色谱耦合质谱的蛋白质组学测量。结果 超声心动图和死后心肌质量显示两性均显着 LV 肥大，这在雌性动物中更为明显（胫骨长度标准化 LV 肌肉质量：+ 17.4% MEx 与 MCo，+ 31.0% FEx 与 FCo）。两性的 LV 收缩性增加至相同程度。3074 种蛋白质的相对表达由蛋白质组学确定。与同性对照的水平相比，男性中 229 种蛋白质的表达和女性中 599 种蛋白质的表达发生了显着变化。根据我们的基因本体分析，女性的生理 LV 重塑的特点是细胞呼吸和脂肪酸氧化中蛋白质的表达增加，而在男性中，与肌动蛋白细胞骨架结合的蛋白质主要增加。结论 我们的数据表明，由规律、平衡的运动引起的生理性左室肥大与心肌蛋白质组的性别特异性变化有关。我们的研究结果有助于理解生理性心肌肥大的发展。女性的生理 LV 重塑的特点是细胞呼吸和脂肪酸氧化中蛋白质的表达增加，而在男性中，与肌动蛋白细胞骨架结合的蛋白质主要增加。结论 我们的数据表明，由规律、平衡的运动引起的生理性左室肥大与心肌蛋白质组的性别特异性变化有关。我们的研究结果有助于理解生理性心肌肥大的发展。女性的生理 LV 重塑的特点是细胞呼吸和脂肪酸氧化中蛋白质的表达增加，而在男性中，与肌动蛋白细胞骨架结合的蛋白质主要增加。结论 我们的数据表明，由规律、平衡的运动引起的生理性左室肥大与心肌蛋白质组的性别特异性变化有关。我们的研究结果有助于理解生理性心肌肥大的发展。平衡运动与心肌蛋白质组的性别特异性变化有关。我们的研究结果有助于理解生理性心肌肥大的发展。平衡运动与心肌蛋白质组的性别特异性变化有关。我们的研究结果有助于理解生理性心肌肥大的发展。