Female aromatase knockout mice lacking estrogens developed 2-fold more cardiac hypertrophy than wild-type females when challenged with isoproterenol, while exercise-induced hypertrophy was unaffected.
The complete lack of estrogens in female mice impairs baseline cardiac function and exacerbates pathological, but not physiological, cardiac hypertrophy, suggesting caution with long-term aromatase inhibitor use.
The incidence of cardiac hypertrophy, an established risk factor for heart failure, is generally lower in women compared with men, but this advantage is lost after menopause. Although it is widely believed that estrogens are cardioprotective, there are contradictory reports, including increased cardiac events in postmenopausal women receiving estrogens and enhanced cardiac protection from ischemic injury in female mice without estrogens. We exposed aromatase knockout (ArKO) mice, which produce no estrogens, to both pathologic and physiologic stimuli. This model allows an investigation into the effects of a complete, chronic lack of estrogens in male and female hearts. At baseline, female ArKO mice had normal-sized hearts but decreased cardiac function and paradoxically increased phosphorylation of many progrowth kinases. When challenged with the pathological stimulus, isoproterenol, ArKO females developed 2-fold more hypertrophy than wild-type females. In contrast, exercise-induced physiological hypertrophy was unaffected by the absence of estrogens in either sex, although running performance was blunted in ArKO females. Thus, loss of estrogen signaling in females, but not males, impairs cardiac function and sensitizes the heart to pathological insults through up-regulation of multiple hypertrophic pathways. These findings provide insight into the apparent loss of cardioprotection after menopause and suggest that caution is warranted in the long-term use of aromatase inhibitors in the setting of breast cancer prevention.
Haines et al. (2012) studied Cardiac hypertrophy. Lack of estrogens (Aromatase knockout) vs. Wild-type mice was evaluated on Cardiac hypertrophy in response to isoproterenol or exercise. Female aromatase knockout mice lacking estrogens developed 2-fold more cardiac hypertrophy than wild-type females when challenged with isoproterenol, while exercise-induced hypertrophy was unaffected.