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Modulation of hypertensive heart disease by estrogen
Insights
Estrogen metabolites stimulate cardiac fibroblast growth and affect calcium channels in heart cells. These findings help explain gender and age differences in hypertensive heart disease.
Area of Science:
- Cardiovascular Biology
- Endocrinology
- Molecular Cardiology
Background:
- Left ventricular hypertrophy (LVH) is a risk factor for morbidity and mortality in hypertensive heart disease.
- Gender-based differences exist in cardiac hypertrophy, with higher mortality in men.
- The role of estrogen in cardiac hypertrophy pathogenesis is not well understood.
Purpose of the Study:
- Investigate the influence of estrogen metabolites on cardiac fibroblast growth.
- Examine the effect of estrogen metabolites on immediate early gene c-Fos expression.
- Determine estrogen's impact on the L-type calcium channel in cardiomyocytes.
Main Methods:
- Incubated neonatal rat cardiac fibroblasts with various estrogen metabolites.
- Measured bromodeoxyuridine incorporation to assess fibroblast growth.
- Assessed L-type calcium channel currents in adult guinea pig cardiomyocytes using whole-cell patch clamp.
Main Results:
- Estrogen metabolites stimulated cardiac fibroblast growth, with 2-hydroxyestrone being the most potent.
- 17 beta-estradiol significantly reduced L-type calcium channel current in cardiomyocytes by approximately 20%.
Conclusions:
- Estrogen exerts both short-term (non-genomic) and long-term (genomic) effects on the heart.
- These estrogen-mediated effects may contribute to gender- and age-based disparities in hypertensive heart disease.
Unlabelled:
Left ventricular hypertrophy is an independent risk factor for morbidity and mortality in patients with hypertensive heart disease. Cardiac hypertrophy, associated with increased cardiac fibrosis and myocardial relaxation impairment, shows gender-based differences with significantly higher mortality in men. The role of estrogen in the pathogenesis of this process is poorly understood. After our previous demonstration that cardiac myocytes and fibroblasts contain functional estrogen receptors, we therefore investigated: 1) the influence of different estrogen metabolites on cardiac fibroblast growth; 2) the influence of different estrogen metabolites on the expression of the immediate early gene c-Fos; 3) the influence of estrogen on the L-type calcium channel in cardiomyocytes.
Methods:
1) Neonatal rat cardiac fibroblasts were incubated with 17 beta-estradiol, estrone, 2-hydroxyestrone, and 2-methoxyestradiol (all 10(-9) M). Bromodeoxyuridine incorporation was measured after 24 h. 2) c-Fos expression was demonstrated by immunoblotting. 3) L-type (Ca2+) current with and without 17 beta-estradiol was assessed in adult guinea pig cardiomyocytes by whole cell patch clamp.
Results:
Cardiac fibroblast growth was stimulated by estrogen metabolites with 2-hydroxyestrone as the most potent activator; in addition, 10(-5) M 17 beta-estradiol reduced the L-type Ca2+ current by about 20% in cardiomyocytes.
Conclusions:
Estrogen induces both short term effects (non-genomic) and long term effects (genomic) on the heart and may therefore account for gender- and age-based differences in hypertensive heart disease.