Estrogen modulation of left ventricular remodeling in the aged heart

Objective: To investigate the effects of estrogen on left ventricle (LV) mass and collagen deposition, and on the expression of receptors for estrogen (ERalpha, ERbeta) and Ang II (AT(2)R, AT(1)R) in the heart of aged female rats. Methods: Aged (similar to12 months old) intact (n=7), ovariectomized plus placebo (OVX, n=7), and estrogen-replaced (E2, n=6) as well as young (similar to3 months old, n=4) female Sprague-Dawley rats were used in this study. After I month of treatment, the left ventricular weight/body weight ratio (LVW/BW), changes in myosin heavy chain expression (MHC), matrix metalloproteinase (MMP)-2 activity, the collagen I/III ratio, and the expression of ERs and Ang II receptors in the LV were evaluated. Results: In aged rats, OVX increased LVW/BW associated with a higher expression of beta-MHC isoform, increased collagen I/III ratio, and decreased MMP-2 activity compared to intact rats. Furthermore, the OVX group had a decrease in ERs alpha and beta as well as AT(2)R but an increase in AT(1)R expression. Estrogen replacement prevented the effects of ovariectomy on heart remodeling as well as increased further expression of ERP and decreased AT(1)R expression. Conclusion: Removal of ovarian hormones increased LV remodeling in the aged rat, which could be attenuated by estrogen replacement. Moreover, regulation of Ang II receptor expression could be a mechanism by which estrogen may modulate heart remodeling. (C) 2003 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.