Estrogen inhibits endoplasmic reticulum stress and ameliorates myocardial ischemia/reperfusion injury in rats by upregulating SERCA2a.

Abstract

BACKGROUND:

The incidence of coronary heart disease (CHD) in premenopausal women is significantly lower than that of men of the same age, suggesting protective roles of estrogen for the cardiovascular system against CHD. This study aimed to confirm the protective effect of estrogen on myocardium during myocardial ischemia/reperfusion (MI/R) injury and explore the underlying mechanisms.

METHODS:

Neonatal rat cardiomyocytes and Sprague-Dawley rats were used in this study. Different groups were treated by bilateral ovariectomy, 17β-estradiol (E2), adenoviral infection, or siRNA transfection. The expression of sarcoplasmic reticulum Ca2+ ATPase pump (SERCA2a) and endoplasmic reticulum (ER) stress-related proteins were measured in each group to examine the effect of different E2 levels and determine the relationship between SERCA2a and ER stress. The cell apoptosis, myocardial infarction size, levels of apoptosis and serum cardiac troponin I, ejection fraction, calcium transient, and morphology changes of the myocardium and ER were examined to verify the effects of E2 on the myocardium.

RESULTS:

Bilateral ovariectomy resulted in reduced SERCA2a levels and more severe MI/R injury. E2 treatment increased SERCA2a expression. Both E2 treatment and exogenous SERCA2a overexpression decreased levels of ER stress-related proteins and alleviated myocardial damage. In contrast, SERCA2a knockdown exacerbated ER stress and myocardial damage. Addition of E2 after SERCA2a knockdown did not effectively inhibit ER stress or reduce myocardial injury.

CONCLUSIONS:

Our data demonstrate that estrogen inhibits ER stress and attenuates MI/R injury by upregulating SERCA2a. These results provide a new potential target for therapeutic intervention and drug discovery in CHD. Video Abstract.

• Authors: Jingwen Chen, Yang Liu, Defeng Pan, Tongda Xu, Yuanyuan Luo, Wanling Wu, Pei Wu, Hong Zhu, Dongye Li
• Journal: Cell communication and signaling : CCS (Cell Commun Signal) Vol. 20 Issue 1 Pg. 38 (03 24 2022) ISSN: 1478-811X [Electronic] England
• PMID: 35331264 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Video-Audio Media)
• Copyright: © 2022. The Author(s).

Chemical References

• Atp2a2 protein, rat
• Estrogens
• Sarcoplasmic Reticulum Calcium-Transporting ATPases

Topics

• Animals
• Apoptosis
• Endoplasmic Reticulum Stress
• Estrogens (pharmacology)
• Female
• Myocardial Reperfusion Injury (drug therapy, metabolism)
• Myocytes, Cardiac
• Rats
• Rats, Sprague-Dawley
• Sarcoplasmic Reticulum Calcium-Transporting ATPases (genetics, metabolism)