2. Academic Validation
  3. Estrogen ameliorates sepsis-induced vascular hyporeactivity in thoracic aorta of female rats via permissive effect of GRα expression

Estrogen ameliorates sepsis-induced vascular hyporeactivity in thoracic aorta of female rats via permissive effect of GRα expression

  • Biochem Biophys Res Commun. 2023 Mar 24;657:108-118. doi: 10.1016/j.bbrc.2023.03.058.
Shan Wang 1,  Jue Wu 2,  Kai Yang 3,  Chunlei Liu 4,  Xin Li 5,  Liben Wu 6,  Xiaoqin Qi 7,  Ruizhi Zhang 8,  Wenfeng Ni 9,  Jinlian Pei 10,  Fangyan Gu 11,  Bing Lu 12,  Yan Wang 13,  Yaping Tian 14
Affiliations

Affiliations

  • 1 Clinical Biobank Center, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, 100853, China. Electronic address: wangshansmmu@126.com.
  • 2 Translational Medicine Research Center, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, 100853, China. Electronic address: wujue0207011@163.com.
  • 3 Prenatal Diagnostic Center, Beijing Obstetrics and Gynecology Hospital, Beijing Maternal and Child Health Care Hospital, Capital Medical University, Beijing, 100026, China. Electronic address: yk19830919@ccmu.edu.cn.
  • 4 Translational Medicine Research Center, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, 100853, China. Electronic address: chunleiliu87@163.com.
  • 5 Translational Medicine Research Center, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, 100853, China. Electronic address: xincoffee@163.com.
  • 6 Clinical Biobank Center, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, 100853, China. Electronic address: 1808257201@qq.com.
  • 7 Clinical Biobank Center, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, 100853, China. Electronic address: 18979938780@163.com.
  • 8 Department of Emergency Medicine, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China. Electronic address: 642643410@qq.com.
  • 9 Clinical Biobank Center, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, 100853, China. Electronic address: nwf1224@163.com.
  • 10 Clinical Biobank Center, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, 100853, China. Electronic address: 18510084466@163.com.
  • 11 Clinical Biobank Center, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, 100853, China. Electronic address: 13681459672@163.com.
  • 12 Department of Emergency Medicine, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China. Electronic address: lbwrr3750533@163.com.
  • 13 Clinical Biobank Center, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, 100853, China. Electronic address: 001wangyan@sina.com.
  • 14 Birth Defect Prevention and Control Technology Research Center, Medical Innovation Research Division, Chinese PLA General Hospital, Beijing, 100853, China. Electronic address: tianyp@301hospital.com.cn.
PMID: 37002984 DOI: 10.1016/j.bbrc.2023.03.058
Abstract

Objective: Estrogen is correlated to the lower mortality and disease severity of female than that of male, which indicates the potential therapeutic role of estrogen supplement therapy in sepsis. The structure of Daidzein is similar to that of 17β estradiol (E2), an estrogen in human body, causing the exogenous Daidzein can interact with Estrogen Receptor as well as E2 in the body. We aim to explore the therapeutic role of estrogen in sepsis-induced vascular dysfunction. Also, we wonder if estrogen regulates blood pressure via glucocorticoid-mediated vascular reactivity.

Methods: Female SD rats received ovariectomy (OVX) to induce estrogen deficiency. After 12 weeks of administration, cecal ligation and puncture (CLP) was used to establish the in vivo model of sepsis. Lipopolysaccharide (LPS) was used to construct the in vitro model of sepsis in vascular smooth muscle cells (VSMCs). E2 and Daidzein were used for estrogen supplement therapy.

Results: E2 and Daidzein significantly inhibited inflammation infiltration and histopathological injury in thoracic aorta in the rat model with CLP. E2 and Daidzein improved carotid pressure and vascular hyporeactivity in sepsis rats with OVX. Importantly, E2 and Daidzein promoted glucocorticoid permissive action and increased Glucocorticoid Receptor α (GRα) expression in thoracic aorta smooth muscle cells. E2 and Daidzein upregulated GRα, and inhibits cytokine production, proliferative phenotype and cell migration in LPS-induced VSMCs.

Conclusion: Estrogen improved vascular hyporeactivity in thoracic aorta induced by sepsis via permissive effect of GRα expression.

Keywords

Estrogen; Glucocorticoid; Sepsis; Vascular dysfunction.

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