Myachina Tatiana A, Butova Xenia A, Simonova Raisa A, Volzhaninov Denis A, Kochurova Anastasia M, Kopylova Galina V, Shchepkin Daniil V, Khokhlova Anastasia D
Institute of Immunology and Physiology UrB RAS, 620049 Yekaterinburg, Russia.
Institute of Natural Sciences and Mathematics, Ural Federal University, 620026 Yekaterinburg, Russia.
Cells. 2025 Apr 8;14(8):561. doi: 10.3390/cells14080561.
17β-estradiol (E2) is the most active metabolite of estrogen with a wide range of physiological action on cardiac muscle. Previous studies have reported E2 effects predominantly for the ventricles, while the E2 impact on the atria has been less examined. In this study, we focused on the direct E2 effects on atrial and ventricular contractility at the cellular and molecular levels. Single atrial and ventricular cardiomyocytes (CM) from adult (24 weeks-old) female Wistar rats were incubated with 10 nM E2 for 15 min. Sarcomere length and cytosolic [Ca] transients were measured in mechanically non-loaded CM, and the tension-length relationship was studied in CM mechanically loaded by carbon fibers. The actin-myosin interaction and sarcomeric protein phosphorylation were analyzed using an in vitro motility assay and gel electrophoresis with Pro-Q Diamond phosphoprotein stain. E2 had chamber-specific effects on the contractile function of CM with a pronounced influence on ventricular CM. The characteristics of [Ca] transients did not change in both atrial and ventricular CM. However, in ventricular CM, E2 reduced the amplitude and maximum velocity of sarcomere shortening and decreased the slope of the passive tension-length relationship that was associated with increased TnI and cMyBP-C phosphorylation. E2 treatment accelerated the cross-bridge cycle of both atrial and ventricular myosin that was associated with increased phosphorylation of the myosin essential light chain. This study shows that E2 impairs the mechanical function of the ventricular myocardium while atrial contractility remains mostly preserved. Hormonal replacement therapy (HRT) with estrogen is by far the most effective therapy for treating climacteric symptoms experienced during menopause. Here we found a chamber specificity of myocardial contractile function to E2 that should be taken into account for the potential side effects of HRT.
17β-雌二醇（E2）是雌激素最具活性的代谢产物，对心肌具有广泛的生理作用。先前的研究主要报道了E2对心室的影响，而对心房的影响则较少研究。在本研究中，我们聚焦于E2在细胞和分子水平上对心房和心室收缩性的直接影响。将成年（24周龄）雌性Wistar大鼠的单个心房和心室心肌细胞（CM）与10 nM E2孵育15分钟。在机械无负荷的CM中测量肌节长度和胞质[Ca]瞬变，并在碳纤维机械加载的CM中研究张力-长度关系。使用体外运动分析和Pro-Q Diamond磷蛋白染色的凝胶电泳分析肌动蛋白-肌球蛋白相互作用和肌节蛋白磷酸化。E2对CM的收缩功能具有腔室特异性影响，对心室CM有显著影响。心房和心室CM中[Ca]瞬变的特征均未改变。然而，在心室CM中，E2降低了肌节缩短的幅度和最大速度，并降低了与TnI和cMyBP-C磷酸化增加相关的被动张力-长度关系的斜率。E2处理加速了心房和心室肌球蛋白的横桥循环，这与肌球蛋白必需轻链磷酸化增加有关。本研究表明，E2损害心室心肌的机械功能，而心房收缩性大多保持不变。雌激素激素替代疗法（HRT）是迄今为止治疗更年期出现的更年期症状最有效的疗法。在这里，我们发现心肌收缩功能对E2具有腔室特异性，这在HRT的潜在副作用方面应予以考虑。
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