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

Area of Science:

• Cardiovascular Biology
• Reproductive Endocrinology
• Biomechanical Engineering

Background:

• Heart failure (HF) is a widespread condition with high mortality, often linked to diastolic dysfunction.
• Post-menopausal women face increased HF risk, yet the impact of menopause on myocardial stiffness remains understudied.
• Menopause-induced hormonal changes may affect cardiac tissue properties, contributing to diastolic dysfunction.

Purpose of the Study:

• To determine if the loss of female hormones affects the Young's modulus (E), a measure of myocardial stiffness.
• To investigate this using a mouse model of menopause induced by ovariectomy (OVX).

Main Methods:

• Ovariectomy (OVX) was performed on mice to induce menopause; a control group underwent sham surgery.
• Fresh left ventricular (LV) myocardial strips were tested for passive stress-stretch relationship to calculate Young's modulus (E).
• Tissues were decellularized to assess the roles of cellular versus extracellular matrix components in stiffness changes.

Main Results:

• Young's modulus (E) in OVX mice was approximately twofold lower than in control (sham-OVX) mice (p < 0.05).
• No significant difference in E was observed between OVX and control groups for decellularized myocardial tissue (p = 0.58).
• This indicates that cellular components, not the extracellular matrix, are primarily responsible for reduced stiffness.

Conclusions:

• Loss of female sexual hormones in the OVX model reduces passive myocardial stiffness.
• This suggests that altered active relaxation mechanisms may compensate for reduced stiffness in post-menopausal women with HF.
• Understanding these hormonal effects is crucial for managing diastolic dysfunction in post-menopausal women.