Journal of Medical Sciences (Jan 2021)

Estrogen deficiency accompanied by oxidative stress sustains heme oxygenase 1 expression in cardiomyocytes of ovariectomized rats

  • Zheng-Zong Lai,
  • Hsiang-Yu Yang,
  • Ping-Nan Chen,
  • Wei-Jou Shih,
  • Hsin-Hsueh Shen,
  • Yen-Mei Lee

DOI
https://doi.org/10.4103/jmedsci.jmedsci_175_20
Journal volume & issue
Vol. 41, no. 3
pp. 146 – 152

Abstract

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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 + E2 (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 E2 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 E2 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 E2 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. E2 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 E2 or tempol administration had no effect on cardiac HO-2 protein expression. Conclusion: E2 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.

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