El Hajj M C, Ninh V K, El Hajj E C, Bradley J M, Gardner J D
Department of Physiology, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana.
Department of Physiology, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana
Am J Physiol Heart Circ Physiol. 2017 Jan 1;312(1):H98-H105. doi: 10.1152/ajpheart.00348.2016. Epub 2016 Oct 21.
We have previously demonstrated the cardioprotective effects of ovarian hormones against adverse ventricular remodeling imposed by chronic volume overload. Here, we assess the estrogen receptor dependence of this cardioprotection. Four groups of female rats were studied: sham-operated (Sham), volume overloaded [aortocaval fistula (ACF)], Sham treated with estrogen receptor antagonist ICI 182,780 (Sham + ICI), and ACF treated with ICI. Cardiac function was assessed temporally using echocardiogram, and tissue samples were collected at 5 days and 6 wk postsurgery. All rats with volume overload had significantly increased cardiac output (96 ± 32 ml/min for ACF and 108 ± 11 ml/min for ACF + ICI vs. 31 ± 2 for Sham, P < 0.05). At 6 wk, volume overload induced significant left ventricular (LV) hypertrophy in both untreated and treated ACF groups. Both ACF groups developed significantly increased LV end-diastolic diameter (LVEDD), indicating LV dilatation, with the ACF + ICI group having the greatest increase (340%, relative to Sham). Ejection fraction was significantly reduced in the ACF + ICI group (23% reduction) at 6 wk postsurgery compared with untreated ACF (P < 0.05). Interstitial collagen staining was significantly reduced by volume overload, with estrogen receptor antagonism causing greater collagen loss at both 5 days and 6 wk postsurgery. Furthermore, volume overload induced a significant increase in LV wall stress only in rats treated with estrogen antagonist. These data indicate that estrogen receptor signaling is essential for sex hormone-dependent cardioprotection against adverse remodeling. The maintenance of myocardial extracellular matrix collagen appears to play a key role in this cardioprotection.
NEW & NOTEWORTHY: We assessed the estrogen receptor (ER) dependence of female-specific cardioprotection using a rat model of chronic volume-overload stress. ER antagonism worsened ventricular wall stress, ventricular dilation, and cardiac dysfunction induced by volume overload. Further, blocking ERs resulted in cardiac remodeling and functional changes similar to that previously found in ovariectomized rats.
我们之前已经证明了卵巢激素对慢性容量超负荷引起的不良心室重塑具有心脏保护作用。在此，我们评估这种心脏保护作用对雌激素受体的依赖性。研究了四组雌性大鼠：假手术组（Sham）、容量超负荷组[主动脉腔静脉瘘（ACF）]、用雌激素受体拮抗剂ICI 182,780处理的假手术组（Sham + ICI）以及用ICI处理的ACF组。使用超声心动图定期评估心脏功能，并在手术后5天和6周收集组织样本。所有容量超负荷的大鼠心输出量均显著增加（ACF组为96±32 ml/min，ACF + ICI组为108±11 ml/min，而Sham组为31±2，P < 0.05）。在6周时，容量超负荷在未处理和处理的ACF组中均诱导了显著的左心室（LV）肥厚。两个ACF组的左心室舒张末期直径（LVEDD）均显著增加，表明左心室扩张，ACF + ICI组增加最大（相对于Sham组增加340%）。与未处理的ACF组相比，ACF + ICI组在手术后6周时射血分数显著降低（降低23%）（P < 0.05）。容量超负荷使间质胶原染色显著减少，雌激素受体拮抗作用在手术后5天和6周均导致更大的胶原丢失。此外，容量超负荷仅在接受雌激素拮抗剂治疗的大鼠中诱导左心室壁应力显著增加。这些数据表明雌激素受体信号传导对于性激素依赖性心脏保护免受不良重塑至关重要。心肌细胞外基质胶原的维持似乎在这种心脏保护中起关键作用。
我们使用慢性容量超负荷应激大鼠模型评估了雌性特异性心脏保护对雌激素受体（ER）的依赖性。ER拮抗作用加重了容量超负荷诱导的心室壁应力、心室扩张和心脏功能障碍。此外，阻断ER导致心脏重塑和功能变化，类似于先前在去卵巢大鼠中发现的情况。
