Passive Stiffness of Left Ventricular Myocardial Tissue Is Reduced by Ovariectomy in a Post-menopause Mouse Model
Passive Stiffness of Left Ventricular Myocardial Tissue Is Reduced by Ovariectomy in a Post-menopause Mouse Model
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DOI：
10.3389/fphys.2018.01545
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发表时间：
2018-11-05
影响因子：
4
通讯作者：
Navajas, Daniel
中科院分区：
文献类型：
--
作者：
Farre, Nuria;Jorba, Ignasi;Navajas, Daniel
背景：心力衰竭（HF）是一种非常普遍的疾病，发病率和死亡率高，通常表现为舒张功能障碍。虽然绝经后妇女发生心衰和舒张功能障碍的风险增加，但对这组患者的临床和实验研究却很少得到重视。具体来说，心肌硬度是否受更年期影响尚不清楚。目的：探讨雌性性激素的缺失是否会改变卵巢切除（OVX）绝经小鼠左室心肌组织的杨氏模量(E)。方法：双侧OVX术后6个月，处死8只小鼠，制备新鲜左室心肌条（类似于8 × 1 × 1 mm），测定其被动应力-拉伸关系。E通过应力-拉伸关系的指数拟合计算。随后，为了评估细胞和细胞外基质成分在确定ovx诱导的E变化中的相对作用，将组织条脱细胞并采用相同的拉伸方案来测量E。结果：OVX小鼠的E （kPa; m +/- SE）比对照组低近2倍（分别为11.7 +/- 1.8和22.1 +/- 4.4,p < 0.05）。脱细胞组织E值组间差异无统计学意义（分别为31.4 +/- 12.05和40.9 +/- 11.5,p = 0.58）。结论：OVX模型中女性性激素的缺失诱导心肌组织被动僵硬度的降低，提示主动松弛在绝经后心衰妇女舒张功能障碍中起平衡作用。
Background: Heart failure (HF) - a very prevalent disease with high morbidity and mortality - usually presents with diastolic dysfunction. Although post-menopause women are at increased risk of HF and diastolic dysfunction, poor attention has been paid to clinically and experimentally investigate this group of patients. Specifically, whether myocardial stiffness is affected by menopause is unknown.Aim: To investigate whether loss of female sexual hormones modifies the Young's modulus (E) of left ventricular (LV) myocardial tissue in a mouse model of menopause induced by ovariectomy (OVX).Methods: After 6 months of bilateral OVX, eight mice were sacrificed, fresh LV myocardial strips were prepared (similar to 8 x 1 x 1 mm), and their passive stress-stretch relationship was measured. E was computed by exponential fitting of the stress-stretch relationship. Subsequently, to assess the relative role of cellular and extracellular matrix components in determining OVX-induced changes in E, the tissues strips were decellularized and subjected to the same stretching protocol to measure E. A control group of eight sham-OVX mice was simultaneously studied.Results: E (kPa; m +/- SE) in OVX mice was similar to twofold lower than in controls (11.7 +/- 1.8 and 22.1 +/- 4.4, respectively; p < 0.05). No significant difference between groups was found in E of the decellularized tissue (31.4 +/- 12.05 and 40.9 +/- 11.5, respectively; p = 0.58).Conclusion: Loss of female sexual hormones in an OVX model induces a reduction in the passive stiffness of myocardial tissue, suggesting that active relaxation should play a counterbalancing role in diastolic dysfunction in post-menopausal women with HF.