title: 17β-Estradiol Enhances Vascular Endothelial Ets-1/miR-126-3p Expression: The Possible Mechanism for Attenuation of Atherosclerosis.
abstract: Endothelial microRNA 126 (miR-126) attenuates the development of atherosclerosis (AS). However, there is no evidence showing the role of miR-126 in estrogen's antiatherogenic effects.
  
  
  
  We hypothesized that 17β-estradiol (E2) modulates miR-126 expression and thus may improve endothelial function and retard AS development.
  
  
  
  This was a prospective cohort study of 12 healthy regularly menstruating female volunteers. ApoE-/- mice were used as the atherosclerosis model and human umbilical vascular endothelial cells (HUVECs) were cultured as the cell model.
  
  
  
  Serum hormones and miR-126-3p levels were measured up to 3 times for 1 cycle. Real-time polymerase chain reaction, histology for atherosclerotic lesions, immunofluorescence, luciferase assay, transfection experiments, cell proliferation, migration and tube formation assay, and western blot were performed.
  
  
  
  Serum concentrations of miR-126-3p in cycling women were higher at the ovulatory and luteal phases than in the follicular phase, and they were positively correlated with E2 values. Administration of miR-126-3p mimics to ApoE-/- mice-attenuated atherogenesis, and antagomir-126-3p partially reversed the protective effect of E2 on atherogenesis. In HUVECs, E2 increased miR-126-3p expression via upregulation of Ets-1 (a transcription factor for miR-126). c-Src/Akt signaling was important for E2-mediated expression of Ets-1/miR-126. E2 decreased expression of miR-126-3p target Spred1 (a protein that inhibits mitogenic signaling). Overexpression of Spred1 partially blocked enhancement of endothelial cell proliferation, migration, and tube formation by E2. Additionally, E2 regulates miR-126-3p-mediated expression of vascular cell adhesion molecule-1 to inhibit monocyte adhesion into HUVECs.
  
  
  
  E2 protection against atherogenesis is possibly mediated by Ets-1/miR-126.
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, People's Republic of China.
authors.forename: Jinzhi
authors.initials: J
authors.lastname: Wei
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, People's Republic of China.
authors.forename: Xiaosa
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Gynecology and Obstetrics, Municipal First People's Hospital of Guangzhou, Guangzhou 510180, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2052, Australia; and.
authors.forename: Weiyu
authors.initials: W
authors.lastname: Chen
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, People's Republic of China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa 56100, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Simoncini
authors.affiliation: Department of Gynecology and Obstetrics, Municipal First People's Hospital of Guangzhou, Guangzhou 510180, People's Republic of China.
authors.forename: Zhengtian
authors.initials: Z
authors.lastname: Gu
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, People's Republic of China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Fu
mesh_terms: D000328:Adult; D000818:Animals; D000070416:Antagomirs / Q000378:metabolism; D001057:Apolipoproteins E; D050197:Atherosclerosis / Q000378:metabolism*; D018929:Cell Culture Techniques; D004195:Disease Models, Animal; D004958:Estradiol / Q000502:physiology*; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008597:Menstrual Cycle / Q000097:blood*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000097:blood / Q000378:metabolism*; D010052:Ovariectomy; D050784:Proto-Oncogene Protein c-ets-1 / Q000378:metabolism*; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D000070416:Antagomirs; D001057:Apolipoproteins E; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D050784:Proto-Oncogene Protein c-ets-1; D004958:Estradiol