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Female sex and estr...
Female sex and estrogen receptor-beta attenuate cardiac remodeling and apoptosis in pressure overload
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Fliegner, D (author)
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Schubert, C (author)
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Penkalla, A (author)
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Witt, H (author)
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Kararigas, G (author)
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Dworatzek, E (author)
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Staub, E (author)
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Martus, P (author)
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Noppinger, PR (author)
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Kintscher, U (author)
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- Gustafsson, JA (author)
- Karolinska Institutet
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Regitz-Zagrosek, V (author)
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(creator_code:org_t)
- American Physiological Society, 2010
- 2010
- English.
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In: American journal of physiology. Regulatory, integrative and comparative physiology. - : American Physiological Society. - 1522-1490 .- 0363-6119. ; 298:6, s. R1597-R1606
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Abstract
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- We investigated sex differences and the role of estrogen receptor-β (ERβ) on myocardial hypertrophy in a mouse model of pressure overload. We performed transverse aortic constriction (TAC) or sham surgery in male and female wild-type (WT) and ERβ knockout (ERβ−/−) mice. All mice were characterized by echocardiography and hemodynamic measurements and were killed 9 wk after surgery. Left ventricular (LV) samples were analyzed by microarray profiling, real-time RT-PCR, and histology. After 9 wk, WT males showed more hypertrophy and heart failure signs than WT females. Notably, WT females developed a concentric form of hypertrophy, while males developed eccentric hypertrophy. ERβ deletion augmented the TAC-induced increase in cardiomyocyte diameter in both sexes. Gene expression profiling revealed that WT male hearts had a stronger induction of matrix-related genes and a stronger repression of mitochondrial genes than WT female hearts. ERβ−/− mice exhibited a different transcriptional response. ERβ−/−/TAC mice of both sexes exhibited induction of proapoptotic genes with a stronger expression in ERβ−/− males. Cardiac fibrosis was more pronounced in male WT/TAC than in female mice. This difference was abolished in ERβ−/− mice. The number of apoptotic nuclei was increased in both sexes of ERβ−/−/TAC mice, most prominent in males. Female sex offers protection against ventricular chamber dilation in the TAC model. Both female sex and ERβ attenuate the development of fibrosis and apoptosis, thus slowing the progression to heart failure.
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Fliegner, D
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Schubert, C
-
Penkalla, A
-
Witt, H
-
Kararigas, G
-
Dworatzek, E
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show more...
-
Staub, E
-
Martus, P
-
Noppinger, PR
-
Kintscher, U
-
Gustafsson, JA
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Regitz-Zagrosek, ...
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show less...
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American journal ...
- By the university
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Karolinska Institutet