Postischemic application of estrogen ameliorates myocardial damage in an in vivo mouse model

Yang Yang, I. Wen Wang, Mark Turrentine, Meijing Wang

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Background: Cardioprotection provided by estrogen has been recognized for many years. It is noteworthy that most of these studies employ a means of preinjury application in experimental research and the preventive usage in clinical studies. Compared to pretreatment, postischemic administration of estrogen will be more practical in treating myocardial ischemia. On the other hand, defect in circadian clock gene period2 (Per2) has been shown to aggravate ischemia-induced heart damage. Given that Per2 expression decreases as a consequence of menopause, in this study, we aim to determine (1) potential improvement of myocardial function by postischemic administration of 17β-estradiol (E2) using an in vivo mouse myocardial ischemia/reperfusion (I/R) model and (2) the role of E2 in regulating myocardial Per2 expression following I/R. Methods: Thirty-minute occlusion of left anterior descending artery followed by 24-h reperfusion was performed on adult C57BL ovariectomized female mice. Groups (n = 3-6/group) were as follows: (1) Sham, (2) I/R + vehicle, and (3) I/R + E2. Vehicle or 0.5 mg/kg of E2 was subcutaneously injected right after 30-min ischemia. Following 24-h reperfusion, myocardial function was determined. Heart tissue was collected for analysis of cleaved caspase-3 and Per2 expression by Western blotting, as well as proinflammatory cytokine production (IL-1β, IL-6, and TNF-α) by enzyme-linked immunosorbent assay. Results: I/R significantly impaired left ventricular function and increased myocardial levels of active caspase-3, IL-1β, and IL-6. Importantly, postischemic treatment of E2 markedly restored I/R-depressed myocardial function, reduced caspase-3 activation, and decreased proinflammatory cytokine production (IL-1β, IL-6, and TNF-α). Intriguingly, a trend of the decreased Per2 level was observed in ovariectomized female hearts subjected to I/R, whereas E2 treatment upregulated myocardial Per2 expression. Conclusions: Our study represents the initial evidence that postischemic administration of E2 effectively preserves the myocardium against I/R injury and this protective effect of E2 may involve upregulation of Per2 in ischemic heart.

Original languageEnglish (US)
Pages (from-to)366-372
Number of pages7
JournalJournal of Surgical Research
Volume231
DOIs
StatePublished - Nov 2018

Keywords

  • Acute postischemic treatment of estrogen
  • Circadian clock gene Per2
  • Coronary artery occlusion
  • Myocardial inflammatory response
  • Myocardial ischemia and reperfusion

ASJC Scopus subject areas

  • Surgery

Fingerprint Dive into the research topics of 'Postischemic application of estrogen ameliorates myocardial damage in an in vivo mouse model'. Together they form a unique fingerprint.

  • Cite this