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17beta-estradiol attenuates pressure overload-induced myocardial hypertrophy through regulating caveolin-3 protein in ovariectomized female rats

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Abstract

Our findings indicate that in ovariectomized female rats abdominal aortic constriction led to significant increases in left ventricular mass, myocyte diameter and heart weight/body weight (HW/BW) value, and decreases in interventricular septal thickness at diastole (IVSd), left ventricular percent fractional shortening (FS) and ejection fraction (EF). These pathophysiological alterations were largely reversed by administration with 17β-estradiol for eight weeks. Furthermore, the enhanced expression of extracellular signal-regulated kinases 1/2 and decreased expression of caveolin-3 were found in left ventricle of AAC group. 17β-estradiol (E2) administration increased the expression of caveolin-3 and reduced the level of ERK phosphorylation in these pressure-overloaded rats. Moreover, in cultured neonatal rat cardiomyocytes, E2 inhibited the hypertrophic response to angiotensin II. This effect was reinforced by the addition of extracellular signal-regulated kinases 1/2 inhibitor PD98059, but was impaired when the cells were pretreated with caveolae disruptor, methyl-β-cyclodextrin (M-β-CD). In conclusion, our data indicate that estrogen attenuates the hypertrophic response induced by pressure overload through down-regulation of extracellular signal-regulated kinases 1/2 phosphorylation and up-regulation of caveolin-3 expression.

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Abbreviations

HW/BW:

Heart weight/body weight

E2 :

17β-estradiol

ERK1/2:

Extracellular signal-regulated kinases 1/2

M-β-CD:

Methyl-β-cyclodextrin

Ang II:

Angiotensin II

LVH:

Left ventricular hypertrophy

ERs:

Estrogen receptors

MAPK:

Mitogen-activated protein kinase

PMSF:

Phenylmethylsulfonyl fluoride

OVX:

Ovariectomized

AAC:

Abdominal aorta constriction operation

LVDd:

Left ventricular end-diastolic diameters

LVDs:

Left ventricular end-systolic diameters

IVSd:

Interventricular septal thickness at diastole

LVPWD:

Left ventricular posterior wall diameter

FS:

Fractional shortening

EF:

Ejection fraction

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Authors and Affiliations

  1. Department of Physiology, ZhongShan School of Medicine, Sun Yat-Sen University, 74 ZhongShan Rd 2, GuangZhou, 510080, People’s Republic of China

    Yu-Hong Cui, Zhi Tan, Xiao-Dong Fu, Qiu-Ling Xiang, Jin-Wen Xu & Ting-Huai Wang

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  1. Yu-Hong Cui
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  2. Zhi Tan
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Correspondence to Ting-Huai Wang.

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Cui, YH., Tan, Z., Fu, XD. et al. 17beta-estradiol attenuates pressure overload-induced myocardial hypertrophy through regulating caveolin-3 protein in ovariectomized female rats. Mol Biol Rep 38, 4885–4892 (2011). https://doi.org/10.1007/s11033-010-0630-0

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  • DOI: https://doi.org/10.1007/s11033-010-0630-0

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