- 期刊
- OpenAccess
Estrogen Deficiency Accompanied by Oxidative Stress Sustains Heme Oxygenase 1 expression in Cardiomyocytes of Ovariectomized Rats
摘要
Background: Estrogen deficiency is one of the main causes of cardiovascular diseases (CVDs) after menopause, accompanied with the upregulation of oxidative stress. Two isoforms of heme oxygenase (HO), HO-1 and HO-2, have been implicated in the cytoprotective effects via the antioxidant and anti-inflammatory capacities. Aims: This study aimed to investigate the time-course of HO-1 and HO-2 expression in the cardiac tissue of ovariectomized rats and whether oxidative stress is involved in the regulation of HO alteration. Methods: Adult female rats were ovariectomized bilaterally to induce estrogen deficiency and randomly divided into (1) Sham, (2) ovariectomy (Ovx), (3) Ovx + E_2 (17β estradiol, 50 μg/kg/day, intramuscular), and (4) Ovx + tempol (1 mM in drinking water, a superoxide dismutase [SOD] mimetic). Rats were sacrificed 12 weeks after Ovx; blood and myocardium samples were collected. Results: Showed that plasma E_2 levels of Ovx and Ovx + tempol groups were significantly reduced as compared to Sham group after 4 weeks of Ovx. Superoxide anion in the cardiac tissue was significantly elevated 2 weeks after Ovx, and the increase was drastically reversed by the treatment with E_2 and tempol. In addition, Ovx rats showed significantly higher levels of oxidized glutathione (GSSG) than those of Sham group, which were also significantly reduced by E_2 and tempol administration. Western blot analysis indicated that HO-1 expression was significantly induced 1 week after Ovx and sustained at high levels until 12 weeks. E_2 replacement did not immediately reverse HO-1 until treatment for 4 weeks as well as tempol administration for 5 weeks. Expression of the constitutive enzymes HO-2 did not show significant differences between Sham and Ovx groups, and E_2 or tempol administration had no effect on cardiac HO-2 protein expression. Conclusion: E_2 deficiency induced upregulation of superoxide anion in the myocardium, which might be the major contributor to the sustained HO-1 expression as adaptive responses to oxidative stress. This study provides new insight into the pathogenesis of CVDs after menopause.
延伸閱讀
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