Kalász Judit, Tóth Enikő Pásztor, Bódi Beáta, Fagyas Miklós, Tóth Attila, Pal Bhattoa Harjit, Vari Sandor G, Balog Marta, Blažetić Senka, Heffer Marija, Papp Zoltán, Borbély Attila
Attila Borbély, University of Debrecen, Institute of Cardiology, Division of Clinical Physiology, Móricz Zsigmond krt. 22, H-4032 Debrecen, Hungary,
Croat Med J. 2014 Jun 1;55(3):239-49. doi: 10.3325/cmj.2014.55.239.
To assess how ovarian-derived sex hormones (in particular progesterone) modify the effects of single acute stress on the mechanical and biochemical properties of left ventricular cardiomyocytes in the rat.
Non-ovariectomized (control, n=8) and ovariectomized (OVX, n=8) female rats were kept under normal conditions or were exposed to stress (control-S, n=8 and OVX-S, n=8). Serum progesterone levels were measured using a chemiluminescent immunoassay. Left ventricular myocardial samples were used for isometric force measurements and protein analysis. Ca(2+)-dependent active force (Factive), Ca(2+)-independent passive force (Fpassive), and Ca(2+)-sensitivity of force production were determined in single, mechanically isolated, permeabilized cardiomyocytes. Stress- and ovariectomy-induced alterations in myofilament proteins (myosin-binding protein C [MyBP-C], troponin I [TnI], and titin) were analyzed by sodium dodecyl sulfate gel electrophoresis using protein and phosphoprotein stainings.
Serum progesterone levels were significantly increased in stressed rats (control-S, 35.6±4.8 ng/mL and OVX-S, 21.9±4.0 ng/mL) compared to control (10±2.9 ng/mL) and OVX (2.8±0.5 ng/mL) groups. Factive was higher in the OVX groups (OVX, 25.9±3.4 kN/m(2) and OVX-S, 26.3±3.0 kN/m(2)) than in control groups (control, 16.4±1.2 kN/m(2) and control-S, 14.4±0.9 kN/m(2)). Regarding the potential molecular mechanisms, Factive correlated with MyBP-C phosphorylation, while myofilament Ca(2+)-sensitivity inversely correlated with serum progesterone levels when the mean values were plotted for all animal groups. Fpassive was unaffected by any treatment.
Stress increases ovary-independent synthesis and release of progesterone, which may regulate Ca(2+)-sensitivity of force production in left ventricular cardiomyocytes. Stress and female hormones differently alter Ca(2+)-dependent cardiomyocyte contractile force production, which may have pathophysiological importance during stress conditions affecting postmenopausal women.
评估卵巢源性性激素（特别是孕酮）如何改变单次急性应激对大鼠左心室心肌细胞力学和生化特性的影响。
将未切除卵巢的（对照组，n = 8）和切除卵巢的（OVX组，n = 8）雌性大鼠置于正常条件下或使其暴露于应激状态（对照组 - S，n = 8和OVX - S组，n = 8）。使用化学发光免疫分析法测定血清孕酮水平。左心室心肌样本用于等长力测量和蛋白质分析。在单个机械分离的透化心肌细胞中测定钙（Ca2 +）依赖性主动力（Factive）、钙（Ca2 +）非依赖性被动力（Fpassive）以及力产生的钙（Ca2 +）敏感性。通过十二烷基硫酸钠凝胶电泳，使用蛋白质和磷蛋白染色分析应激和卵巢切除诱导的肌丝蛋白（肌球蛋白结合蛋白C [MyBP - C]、肌钙蛋白I [TnI]和肌联蛋白）的改变。
与对照组（10±2.9 ng/mL）和OVX组（2.8±0.5 ng/mL）相比，应激大鼠（对照组 - S，35.6±4.8 ng/mL和OVX - S，21.9±4.0 ng/mL）的血清孕酮水平显著升高。OVX组（OVX，25.9±3.4 kN/m²和OVX - S，26.3±3.0 kN/m²）的Factive高于对照组（对照组，16.4±1.2 kN/m²和对照组 - S，14.4±0.9 kN/m²）。关于潜在的分子机制，当绘制所有动物组的平均值时，Factive与MyBP - C磷酸化相关，而肌丝钙（Ca2 +）敏感性与血清孕酮水平呈负相关。Fpassive不受任何处理的影响。
应激增加了不依赖卵巢的孕酮合成和释放，这可能调节左心室心肌细胞力产生的钙（Ca2 +）敏感性。应激和女性激素以不同方式改变钙（Ca2 +）依赖性心肌细胞收缩力的产生，这在影响绝经后妇女的应激条件下可能具有病理生理学意义。
