Chronic hypoestrogenism promotes apoptotic death in cardiac myocytes of the left ventricular myocardium

Abstract

This study characterizes the remodeling of the left ventricular (LV) myocardium in rats with surgically‐induced hypoestrogenism (hypo‐E). The research was done on 15 adult outbred female rats: 10 rats underwent bilateral ovariectomy, while 5 rats served as a control. The LV myocardium was examined with light microscopy, immunocytochemistry (Ñas‐3 and Bcl‐2 protein expression) and morphometry on 2, 6 and 12 months (m) after the surgery. We found that the volume fraction of myocardial interstitial tissue was significantly increased in all hypo‐E rats (38.9±5.4% at 2m, 48.8±6.4% at 6m, 35.3±5.3% at 12m vs. 15.6±2.6% in control, đ<0.05). At the same time, after an initial increase in cardiac myocyte (CM) diameter at 6m of hypo‐E (9.96±1.57μm vs. 8.68±1.64 μm in control, đ<0.05), the average CM diameter was reduced to 7.6±1.7 μm at 12m, suggestive of CM atrophy. The latter observation was further confirmed by the marked decrease in CM volume fraction in these rats (64.6±4.8% vs. 84.2±2.51% in control). Furthermore, the progressive reduction of Bcl‐2+CM in hypo‐E rats (0.21±0.04% at 6m and 0.17±0.01%, at 12m vs. 0.6±0.03% at 2m, p<0.05) in concert with the increase of Cas‐3+ cells (0.4±0.01% at 6m and 0.38±0.05%, at 12m vs. 0.22±0.03% at 2m, p<0.05) has suggested the gradual increase in CM apoptosis. Thus, our data demonstrated that chronic hypo‐E in rats was associated with a significant increase in apoptotic death of LV myocytes.