In:
Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 117, No. suppl_1 ( 2015-07-17)
Abstract:
The steroid hormone 17β-estradiol (E2) regulates several biological processes. In contrast to its anti-hypertrophic effects under pressure overload, we recently found that E2 induced physiological hypertrophic growth in healthy C57Bl/6J mice but not C57Bl/6N mice. Here, we aimed at the characterization of the effects of E2 in C57Bl/6N mice and tested the hypothesis that β-catenin mediates these E2 effects. Following ovariectomy, 2-month-old C57Bl/6N wild-type and cardiac-specific β-catenin-deleted (β-cat Δex2-6 ) mice were randomized to an E2-containing or soy-free (control, CON) diet ( n = 7-13/group). Cardiac function was examined by echocardiography following established procedures. The 3-month physiological dose of E2 led to a higher relative uterus weight compared with CON ( P 〈 0.001) in both WT and β-cat Δex2-6 mice. The relative heart weight was significantly reduced by E2 compared with CON in WT mice ( P 〈 0.001), while there was no significant effect in β-cat Δex2-6 mice. Cardiomyocyte cross-sectional area was also significantly decreased by E2 ( n = 5-7/group; P 〈 0.001) compared with CON in WT mice, while there was no significant effect in β-cat Δex2-6 mice. Echocardiography revealed a significant decrease in septum width ( P 〈 0.001) and posterior wall thickness ( P 〈 0.01) in E2 treated WT mice compared with CON, while there was no significant effect in β-cat Δex2-6 mice ( n = 8/group). These E2-induced structural changes in WT mice were accompanied by a significant decrease in cardiac function, namely a 23% decrease in fractional shortening compared with CON ( P 〈 0.05), while there was no significant effect in β-cat Δex2-6 mice. Immunoblotting revealed a significant increase in the levels of the ubiquitin ligase and key regulator of proteasome-dependent protein degradation muscle-specific RING finger protein 1 (MuRF1) by E2 compared with CON in WT mice ( P 〈 0.05), while there was no significant effect in β-cat Δex2-6 mice. Although we hypothesized increased autophagic activity, we found no effect on the autophagy-related protein LC3 in WT or β-cat Δex2-6 mice. In conclusion, our surprising findings show that E2 leads to cardiac atrophy and dysfunction in C57Bl/6N mice via a β-catenin mechanism seemingly in an autophagy-independent manner.
Type of Medium:
Online Resource
ISSN:
0009-7330
,
1524-4571
DOI:
10.1161/res.117.suppl_1.36
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2015
detail.hit.zdb_id:
1467838-X
