Effects of estrogen, an ERα agonist and raloxifene on pressure overload induced cardiac hypertrophy.
The aim of this study was to investigate the effects of 17β-estradiol (E2), the selective ERα agonist 16α-LE2, and the selective estrogen receptor modulator (SERM) raloxifene on remodeling processes during the development of myocardial hypertrophy (MH) in a mouse model of pressure overload. Myocardi...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3515519?pdf=render |
| _version_ | 1818970246754598912 |
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| author | Christina Westphal Carola Schubert Katja Prelle Adam Penkalla Daniela Fliegner George Petrov Vera Regitz-Zagrosek |
| author_facet | Christina Westphal Carola Schubert Katja Prelle Adam Penkalla Daniela Fliegner George Petrov Vera Regitz-Zagrosek |
| author_sort | Christina Westphal |
| collection | DOAJ |
| description | The aim of this study was to investigate the effects of 17β-estradiol (E2), the selective ERα agonist 16α-LE2, and the selective estrogen receptor modulator (SERM) raloxifene on remodeling processes during the development of myocardial hypertrophy (MH) in a mouse model of pressure overload. Myocardial hypertrophy in ovariectomized female C57Bl/6J mice was induced by transverse aortic constriction (TAC). Two weeks after TAC, placebo treated mice developed left ventricular hypertrophy and mild systolic dysfunction. Estrogen treatment, but not 16α-LE2 or raloxifene reduced TAC induced MH compared to placebo. E2, 16α-LE2 and raloxifene supported maintenance of cardiac function in comparison with placebo. Nine weeks after induction of pressure overload, MH was present in all TAC groups, most pronounced in the raloxifene treated group. Ejection fraction (EF) was decreased in all animals. However, 16α-LE2 treated animals showed a smaller reduction of EF than animals treated with placebo. E2 and 16α-LE2, but not raloxifene diminished the development of fibrosis and reduced the TGFβ and CTGF gene expression. Treatment with E2 or 16α-LE2 but not with raloxifene reduced survival rate after TAC significantly in comparison with placebo treatment. In conclusion, E2 and 16α-LE2 slowed down the progression of MH and reduced systolic dysfunction after nine weeks of pressure overload. Raloxifene did not reduce MH but improved cardiac function two weeks after TAC. However, raloxifene was not able to maintain EF in the long term period. |
| first_indexed | 2024-12-20T14:33:26Z |
| format | Article |
| id | doaj.art-ebdb78c9a3e14745b8ba99cfab8bb1db |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T14:33:26Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ebdb78c9a3e14745b8ba99cfab8bb1db2022-12-21T19:37:32ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01712e5080210.1371/journal.pone.0050802Effects of estrogen, an ERα agonist and raloxifene on pressure overload induced cardiac hypertrophy.Christina WestphalCarola SchubertKatja PrelleAdam PenkallaDaniela FliegnerGeorge PetrovVera Regitz-ZagrosekThe aim of this study was to investigate the effects of 17β-estradiol (E2), the selective ERα agonist 16α-LE2, and the selective estrogen receptor modulator (SERM) raloxifene on remodeling processes during the development of myocardial hypertrophy (MH) in a mouse model of pressure overload. Myocardial hypertrophy in ovariectomized female C57Bl/6J mice was induced by transverse aortic constriction (TAC). Two weeks after TAC, placebo treated mice developed left ventricular hypertrophy and mild systolic dysfunction. Estrogen treatment, but not 16α-LE2 or raloxifene reduced TAC induced MH compared to placebo. E2, 16α-LE2 and raloxifene supported maintenance of cardiac function in comparison with placebo. Nine weeks after induction of pressure overload, MH was present in all TAC groups, most pronounced in the raloxifene treated group. Ejection fraction (EF) was decreased in all animals. However, 16α-LE2 treated animals showed a smaller reduction of EF than animals treated with placebo. E2 and 16α-LE2, but not raloxifene diminished the development of fibrosis and reduced the TGFβ and CTGF gene expression. Treatment with E2 or 16α-LE2 but not with raloxifene reduced survival rate after TAC significantly in comparison with placebo treatment. In conclusion, E2 and 16α-LE2 slowed down the progression of MH and reduced systolic dysfunction after nine weeks of pressure overload. Raloxifene did not reduce MH but improved cardiac function two weeks after TAC. However, raloxifene was not able to maintain EF in the long term period.http://europepmc.org/articles/PMC3515519?pdf=render |
| spellingShingle | Christina Westphal Carola Schubert Katja Prelle Adam Penkalla Daniela Fliegner George Petrov Vera Regitz-Zagrosek Effects of estrogen, an ERα agonist and raloxifene on pressure overload induced cardiac hypertrophy. PLoS ONE |
| title | Effects of estrogen, an ERα agonist and raloxifene on pressure overload induced cardiac hypertrophy. |
| title_full | Effects of estrogen, an ERα agonist and raloxifene on pressure overload induced cardiac hypertrophy. |
| title_fullStr | Effects of estrogen, an ERα agonist and raloxifene on pressure overload induced cardiac hypertrophy. |
| title_full_unstemmed | Effects of estrogen, an ERα agonist and raloxifene on pressure overload induced cardiac hypertrophy. |
| title_short | Effects of estrogen, an ERα agonist and raloxifene on pressure overload induced cardiac hypertrophy. |
| title_sort | effects of estrogen an erα agonist and raloxifene on pressure overload induced cardiac hypertrophy |
| url | http://europepmc.org/articles/PMC3515519?pdf=render |
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