title: Differential proteomic analysis of umbilical artery tissue from preeclampsia patients, using iTRAQ isobaric tags and 2D nano LC-MS/MS.
abstract: Epidemiological studies suggest that the impact of preeclampsia does not only affect the mother but also the children. We know that adverse events in utero may predispose individuals to premature cardiovascular disease in adulthood, but we do not know the mechanisms. To gain insights into the mechanisms of cardiovascular dysfunction in the offspring of preeclampsia, we employed a global stable isotope labeled profiling strategy using iTRAQ reagents, followed by 2D-LC-MS/MS. We identified 1521 non-redundant proteins, and 1496 of these were quantified. Further analysis identified 53 differentially expressed proteins in umbilical artery; 22 proteins were up-regulated and 31 proteins were down-regulated. K-means clustering analysis showed that there was a specific protein expression profile in the umbilical artery which could distinguish between normal and preeclampsia patients. These 53 proteins were analyzed by Ingenuity Pathway Analysis (IPA) and were found to play important roles in the angiogenesis, vasculogenesis, and development of the cardiovascular system. In addition, the differential expression of three cardiovascular relative proteins (aldose reductase, fibronectin-1, fibrillin-1) was independently verified using western blot. These results may supply new insights into the mechanisms of vascular dysfunction in the offspring of preeclampsia patients.
  
  
  CONCLUSIONS
  Increasing evidence suggests that the children who were exposed to preeclampsia in utero have an increased cardiovascular risk, and vascular dysfunction has been found in some children born of preeclampsia. However, the mechanism remains largely unknown. In this study, we identified 1521 non-redundant proteins, and 1496 of these were quantified. Further analysis identified 53 differentially expressed proteins in the umbilical artery from preeclampsia patients; 22 proteins were up-regulated and 31 proteins were down-regulated. Some of these differentially expressed proteins have been shown to play important roles in cardiovascular system development. Our results provide new insights into the potential mechanisms underlying the changed blood pressure of offspring of mothers with preeclampsia, and, the elevation of their risk of cardiovascular abnormality in later life.
authors.affiliation: The Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, China; Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Pan
authors.affiliation: The Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, China; Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Meng-Xi
authors.initials: MX
authors.lastname: Guo
authors.affiliation: The Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, China.
authors.forename: Yi-Meng
authors.initials: YM
authors.lastname: Xiong
authors.affiliation: The Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, China; Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
authors.affiliation: The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jun-Yu
authors.initials: JY
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, China; Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Gao
authors.affiliation: The Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, China.
authors.forename: Zhang-Hong
authors.initials: ZH
authors.lastname: Ke
authors.affiliation: The Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, China.
authors.forename: Gu-Feng
authors.initials: GF
authors.lastname: Xu
authors.affiliation: The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Ya-Jing
authors.initials: YJ
authors.lastname: Tan
authors.affiliation: The Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, China; Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou, China. Electronic address: shengjz@zju.edu.cn.
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Sheng
authors.affiliation: The Key Laboratory of Reproductive Genetics, Ministry of Education (Zhejiang University), Hangzhou, China; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China. Electronic address: huanghefg@hotmail.com.
authors.forename: He-Feng
authors.initials: HF
authors.lastname: Huang
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D014469:Umbilical Arteries / Q000378:metabolism*
chemical_list: D020543:Proteome
keywords: Gamete and embryo-fetal origins of adult diseases; Offspring; Preeclampsia; Umbilical artery; iTRAQ