Passive Stiffness of Left Ventricular Myocardial Tissue Is Reduced by Ovariectomy in a Post-menopause Mouse Model

绝经后小鼠模型中卵巢切除术可降低左心室心肌组织的被动僵硬程度

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作者:Núria Farré, Ignasi Jorba, Marta Torres, Bryan Falcones, Julio Martí-Almor, Ramon Farré, Isaac Almendros, Daniel Navajas

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).

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.

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.

Methods

After 6 months of bilateral OVX, eight mice were sacrificed, fresh LV myocardial strips were prepared (∼8 × 1 × 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 ∼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).

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