Estrogens mediate cardiac hypertrophy in a stimulus-dependent manner

Area of Science:

• Cardiovascular biology
• Endocrinology
• Physiology

Background:

• Cardiac hypertrophy is a risk factor for heart failure, generally less common in women than men.
• This cardioprotective advantage in women diminishes post-menopause, despite the common belief in estrogen's protective role.
• Contradictory findings exist regarding estrogen's effect on cardiac events and ischemic injury.

Purpose of the Study:

• To investigate the impact of a complete, chronic absence of estrogens on male and female hearts.
• To examine the effects of pathologic and physiologic stimuli in estrogen-deficient mice.

Main Methods:

• Utilized aromatase knockout (ArKO) mice, which lack estrogen production.
• Exposed ArKO and wild-type mice to isoproterenol (pathologic stimulus) and exercise (physiologic stimulus).
• Assessed cardiac function, heart size, and hypertrophic pathway signaling.

Main Results:

• Female ArKO mice exhibited decreased cardiac function and increased progrowth kinase signaling at baseline.
• ArKO females developed significantly more cardiac hypertrophy in response to isoproterenol compared to controls.
• Exercise-induced hypertrophy was not affected by estrogen absence, though running performance was reduced in ArKO females.

Conclusions:

• Loss of estrogen signaling in females impairs cardiac function and increases susceptibility to pathological insults.
• Estrogen deficiency up-regulates cardiac hypertrophic pathways, potentially explaining post-menopausal heart disease.
• Findings suggest caution regarding long-term aromatase inhibitor use for breast cancer prevention.