title: ERβ expression in the endothelium ameliorates ischemia/reperfusion-mediated oxidative burst and vascular injury.
abstract: Estrogen and estrogen receptors (ERs) have been reported to play protective roles in ischemia/reperfusion (I/R)-mediated injury, but the detailed mechanism remains to be fully understood. Nitric oxide (NO) and reactive oxygen species (ROS) also play important roles in the I/R process; however, due to the lack of sensitive and reproducible in vivo monitoring systems, we still do not have direct evidence for the effect of NO and ROS in vivo. In this study, we have established reliable in vivo monitoring systems to measure the variations in circulating ROS and NO during the I/R. We found that during the first few minutes of post-ischemia reperfusion, an oxidative burst occurred concurrent with a rapid loss of NO. Expression of ERβ in the endothelium reduced these effects that accompanied an attenuation in myocardial infarction and vascular damage. Further investigation showed that Tie2-driven lentivirus delivery of ERβ to the vascular wall in rats increased the expression of its target genes in the endothelium, including ERRα, SOD2 and eNOS. These changes modulate ROS generation, DNA damage, and mitochondrial function in rat endothelial cells. We also found that ERβ expression in the endothelium reduced ROS generation and restored mitochondrial function in cardiomyocytes; this may be due to ERβ-mediated NO formation and its high diffusibility to cardiomyocytes. We conclude that ERβ expression in the endothelium ameliorates ischemia/reperfusion-mediated oxidative burst and vascular injury.
authors.affiliation: Tongji Wenchang Hospital, Huazhong University of Science and Technology, Wenchang 571321, China; Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Zhaoyu
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Tongji Wenchang Hospital, Huazhong University of Science and Technology, Wenchang 571321, China.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Ding
authors.affiliation: Tongji Wenchang Hospital, Huazhong University of Science and Technology, Wenchang 571321, China.
authors.forename: Laxi
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Qiaomei
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Ziyun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Lab of Analytical Chemistry, Department of Chemistry, University of Ioannina, Ioannina, 45110 Greece.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Vlessidis
authors.affiliation: Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport 71130 LA, USA.
authors.forename: Tak Yee
authors.initials: TY
authors.lastname: Aw
authors.affiliation: Tongji Wenchang Hospital, Huazhong University of Science and Technology, Wenchang 571321, China; Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: liuzhengxiang@hotmail.com.
authors.forename: Zhengxiang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Tongji Wenchang Hospital, Huazhong University of Science and Technology, Wenchang 571321, China; Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: dachun927@hotmail.com.
authors.forename: Dachun
authors.initials: D
authors.lastname: Yao
mesh_terms: D000818:Animals; D004249:DNA Damage / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D047629:Estrogen Receptor beta / Q000235:genetics*; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D009203:Myocardial Infarction / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics*; D015427:Reperfusion Injury / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016897:Respiratory Burst / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics*; D057772:Vascular System Injuries / Q000235:genetics / Q000378:metabolism; D000097983:ERRalpha Estrogen-Related Receptor; D000099156:Superoxide Dismutase 2
chemical_list: D047629:Estrogen Receptor beta; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D017382:Reactive Oxygen Species; D011960:Receptors, Estrogen; D013482:Superoxide Dismutase; D000097983:ERRalpha Estrogen-Related Receptor; D000099156:Superoxide Dismutase 2
keywords: Mitochondria; Nitric oxide; Oxidative stress; SOD2; Vascular biology