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Published on: September 23, 2014
Differences in Androgen Receptor Expression in Human Heart Tissue in Various Types of Cardiomyopathy and in Aortic
Katja Eildermann1, Sabrina Goldmann1, Ulrich Krause1
1Department of Pediatric Cardiology and Intensive Care Medicine, Georg-August-University Goettingen, 37077 Goettingen, Germany.
Insights
Androgen receptor (AR) protein and mRNA are regulated differently in various heart diseases, particularly in cardiac hypertrophy. This suggests a potential role for AR in the pathology of heart conditions.
Area of Science:
- Cardiovascular Biology
- Endocrinology
- Molecular Cardiology
Background:
- Sex hormones like estrogen and testosterone influence heart disease outcomes.
- Estrogen receptor roles in cardiac disease are known, but androgen receptor (AR) research is limited.
- This study investigates AR expression in human heart tissue across various cardiac conditions.
Purpose of the Study:
- To examine androgen receptor (AR) protein and mRNA expression in human myocardium.
- To compare AR expression in non-failing hearts versus hearts with aortic stenosis, hypertrophic cardiomyopathy, dilated cardiomyopathy, and ischemic cardiomyopathy.
- To explore potential sex-specific differences in AR expression.
Main Methods:
- Western blotting was used to quantify full-length AR and AR45 protein levels in myocardial samples.
- Quantitative reverse transcription PCR (qRT-PCR) assessed full-length AR and AR45 mRNA expression.
- Immunohistochemistry localized AR protein in myocardial tissue from hypertrophic and aortic stenosis patients.
Main Results:
- Full-length AR protein was elevated in aortic stenosis and hypertrophic cardiomyopathy compared to other conditions.
- AR45 protein was more abundant in hypertrophic cardiomyopathy than dilated cardiomyopathy.
- While AR protein levels varied by disease, AR mRNA levels showed different patterns, and immunohistochemistry revealed stronger nuclear AR in males.
Conclusions:
- Androgen receptor (AR) expression is regulated in a disease-specific manner in the human heart, especially in cardiac hypertrophy.
- Findings suggest a potential role for AR in the pathogenesis of cardiac hypertrophy.
- Further research is warranted to elucidate the precise function of AR in cardiovascular disease.
Abstract:
Background: Sex-specific differences in heart disease outcomes are influenced by the levels of the steroid hormones, estrogen and testosterone. While the roles of estrogen receptors in cardiac disease are well-studied in animals and humans, respective research on androgen receptors (AR) is limited. Here we investigate AR protein and mRNA expression in human myocardium of various cardiac diseases. Methods: AR expression was analyzed by western blotting in myocardium from human non-failing hearts (NF, n = 6) and patients with aortic stenosis (AS, n = 6), hypertrophic cardiomyopathy (HCM, n = 7), dilated cardiomyopathy (DCM, n = 7), and ischemic cardiomyopathy (ICM, n = 7). Using an AR45-specific antibody, a subsequent western blot assessed samples from male and female patients with HCM (n = 10) and DCM (n = 10). The same sample set was probed for full-length AR and AR45 mRNA expression. Immunohistochemistry (IHC) localized AR in myocardium from HCM and AS hearts. Results: Full-length AR was notably enriched in AS and HCM hearts compared to ICM, DCM, and NF. Similarly, AR45 was more abundant in HCM than in DCM. In contrast to the pattern observed for AR protein, full-length AR mRNA levels were lower in HCM compared to DCM, with no discernible difference for the AR45 isoform. Although gender differences in AR expression were not detected in western blots or qRT-PCR, IHC showed stronger nuclear AR signals in males than in females. Conclusions: Our findings indicate disease-specific regulation of AR mRNA and/or AR protein in cardiac hypertrophy, underscoring a potential role in this cardiac pathology.
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