17β-estradiol reduces cardiac hypertrophy mediated through the up-regulation of PI3K/Akt and the suppression of calcineurin/NF-AT3 signaling pathways in rats

Chieh Hsi Wu, Jer Yuh Liu, Jia Ping Wu, Yi Hsien Hsieh, Chung Jung Liu, Jin Ming Hwang, Shin Da Lee, Li Mien Chen, Mu Hsin Chang, Wei Wen Kuo, Jyh Cherng Shyu, Jen Hsiang Tsai, Chih Yang Huang

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

This study was designed to determine the effects of 17β-estradiol (E2) in overcoming the cardiac over-loading and cardiac fibrosis in rats. E2 (100 ng/kg) or oil was applied in female Sprague-Dawley rats with or without bilateral ovariectomy and with or without coarctation of the abdominal aorta after 4 or 8 days. By post-operative day 4, the heart weight, the left ventricular weight, the latent form of MMP-2 in rat hearts with or without the ovary intact had significantly increased while these changes were reversed after E2 treatment. Although animals with the ovaries intact overcame the hypertrophic effects and the consumption of MMP-2, these effects were not restored in ovariectomized animals in which more fibrosis could be found by day 8. Among the IGF-I signaling, the levels of IGF-I, the activities of PI3K-Akt for cardiomyocyte survival, and MEK-ERKs for non-cardiomyocyte proliferation pathways had significantly increased by day 4. These increasing trends were enhanced by E2 treatment. However, down-regulation was only observed on day 8 in ovariectomized animals. Similarly, elevated expressions of the steady-state mRNA of IGF-I, IGF-IR, and Cox vb were observed on day 4 in animals with the ovaries intact and these expressions were enhanced by E2 treatment. In contrast, down-regulation on day 8 in ovariectomized animals was not enhanced by E2. The calcineurin/NFAT-3 pathway was suppressed on day 4 but was elevated on day 8 in ovariectomized animals. These findings indicate that signaling pathways may be plausible mechanisms for the cardiac protective effects of E2 administration.

Original languageEnglish
Pages (from-to)347-356
Number of pages10
JournalLife Sciences
Volume78
Issue number4
DOIs
Publication statusPublished - Dec 12 2005
Externally publishedYes

Keywords

  • 17β-estradiol
  • Abdominal aorta coarctation
  • Calcineurin/NFAT-3 pathway IGF-I signaling
  • Left ventricle hypertrophy

ASJC Scopus subject areas

  • Pharmacology

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