title: Prenatal hypoxia promotes atherosclerosis via vascular inflammation in the offspring rats.
abstract: BACKGROUND
  Hypoxia is a critical contributor to increased risks of cardiovascular diseases, including atherosclerosis, but the detailed mechanism that hypoxia leads to atherosclerosis remains unknown.
  
  
  METHODS
  Pregnant rats were treated with hypoxia (10.5% oxygen) during pregnancy, and HUVEC cells treated with 1% of oxygen. Blood lipids were tested at fetal stage and adult stage of offspring rats; the level of pro-inflammatory cytokines of HUVEC and offspring rats were investigated, and HIF-1α and NFκB mRNA level were also measured by Q-PCR and Elisa.
  
  
  RESULTS
  We found that TC, LDL-C, ox-LDL-C, and the receptors of ox-LDL-C (lox-1) of the adult offspring were significantly higher than that of the control, while HDL-C was significantly reduced in hypoxia group. The internal elastic lamina was blocked by smooth muscle cells; and the migration of smooth muscle cells into the intima were observed in hypoxia offspring. Luciferase reporter gene experiment showed that HIF-1α activated NFκB transcription at four discrete binding sites of NFκBp65 promoter, although there was no obvious difference among the four discrete binding sites. Using transfection of pCDNA3.1-HIF-1α on HUVEC cells, HIF-1α significantly activated NFκB transcription at hypoxic conditions (1% O2), and concurrent with increased expression of IL-1β and TNF-α.
  
  
  CONCLUSIONS
  Hypoxia during pregnancy activated NFκB transcription to induce pro-inflammatory cytokines, leading to the early stage of atherosclerosis.
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
authors.forename: Pengjie
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Emergency Department, First Hospital of Soochow University, Suzhou, China.
authors.forename: Xionghui
authors.initials: X
authors.lastname: Chen
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
authors.forename: Qinqin
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
authors.forename: Lingjun
authors.initials: L
authors.lastname: Li
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
authors.forename: Xiuwen
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
authors.forename: Juanxiu
authors.initials: J
authors.lastname: Lv
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Sun
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
authors.forename: Caiping
authors.initials: C
authors.lastname: Mao
authors.affiliation: Institute for Fetology, First Hospital of Soochow University, Suzhou, China; Center for Prenatal Biology, Loma Linda University, CA, USA. Electronic address: xuzhice@suda.edu.cn.
authors.forename: Zhice
authors.initials: Z
authors.lastname: Xu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology* / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D000860:Hypoxia / Q000097:blood / Q000150:complications*; D008055:Lipids / Q000097:blood*; D011247:Pregnancy; D011270:Pregnancy, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D014657:Vasculitis / Q000097:blood / Q000150:complications* / Q000473:pathology
chemical_list: D008055:Lipids
keywords: Atherosclerosis; Inflammation; Prenatal hypoxia; Pro-inflammatory cytokines