16α-OHE1, a novel oestrogen metabolite, attenuates dysfunction of left ventricle contractility via regulation of autophagy after myocardial ischemia and reperfusion

作者：Yin, Ze-Yuan; Fu, Tong; He, Shi-Min; Fu, Lu; Li, Xi-Zhi; Xu, Liu; Du, Lei; Yang, Ting-Ting; Zhu, Xia; Wang, Cheng; Qiao, Wei-Li; Tang, Zi-Qing; Zhang, Xiao-Yan; Li, Kun; Zhang, Xin-Yuan; Gong, Zheng; Zhou, Xue-Yan^*; Zhang, Bei^*; Sun, Hong^*

来源：International Journal of Cardiology, 2023, 388: 131123.

DOI：10.1016/j.ijcard.2023.131123

• Myocardial ischemia/reperfusion injury
• 16 alpha-OHE1
• Oestrogen metabolites
• Autophagy
• Left ventricle contractility

Background: Myocardial ischemia-reperfusion (MI/R) can exacerbate the initial cardiac damage in the myocardial functional changes, including dysfunction of left ventricular contractility. Oestrogen has been proven to protect the cardiovascular system. However, whether the oestrogen or its metabolites play the main role in attenuating dysfunction of left ventricular contractility is unknown.Methods and results: This study used the LC-MS/MS to detect oestrogen and its metabolites in clinical serum samples (n = 62) with heart diseases. After correlation analysis with markers of myocardial injury including cTnI (P < 0.01), CK-MB (P < 0.05), and D-Dimer (P < 0.001), 16 alpha-OHE1 was identified. The result from LC-MS/MS in female and ovariectomised (OVX) rat serum samples (n = 5) matched the findings in patients. In MI/R model of animal, the recovery of left ventricular developed pressure (LVDP), rate pressure product (RPP), dp/dt(max) and dp/dt(min) after MI/R in OVX or male group were worsened than those in female group. Also, the infarction area of OVX or male group was larger than that in females (n = 5, p < 0.01). Furthermore, LC3 II in the left ventricle of OVX and male group was lower than that in females (n = 5, p < 0.01) by immunofluorescence. In H9C2 cells, after the application of 16 alpha-OHE1, the number of autophagosomes was further increased and other organelles improved in MI/R. Simultaneously, LC3 II, Beclin1, ATG5, and p-AMPK/AMPK were increased, and p-mTOR/ mTOR was decreased (n = 3, p < 0.01) by Simple Western.Conclusion: 16 alpha-OHE1 could attenuate left ventricle contractility dysfunction via autophagy regulation after MI/ R, which also offered fresh perspectives on therapeutical treatment for attenuating MI/R injury.

• 单位
  南方医科大学