title: A longitudinal study of maternal endothelial function, inflammatory response and uterine artery blood flow during the second half of pregnancy.
abstract: BACKGROUND
  The objective of this study was to investigate serial changes in maternal endothelial function, inflammatory response and uterine artery blood flow in normal pregnancy, and to explore their inter-relation.
  
  
  METHODS
  In this prospective longitudinal observational study, 53 women with uncomplicated pregnancies were examined at 4-weekly intervals (248 observations) during 22-40 weeks of gestation. Uterine artery blood flow was measured using Doppler ultrasonography. Maternal endothelial function was assessed by flow-mediated vasodilatation (FMD) of the brachial artery. Circulating endothelial progenitor cells (EPC), defined as CD34(+) CD133(+) VEGFR2(+) cells, were quantified by flow cytometry. Biomarkers of inflammation, such as leptin and high sensitivity C-reactive protein (hsCRP), were measured in plasma samples. Multilevel modeling was used to investigate gestational-age-associated serial changes.
  
  
  RESULTS
  The EPC increased from 6.5 to 12.3 per million mononuclear cells (p < 0.01) and FMD decreased from 16.3 to 13.4% (p = 0.20). Leptin increased from 18 to 22 ng/mL (p < 0.01), and hsCRP did not change significantly (p = 0.61). There was no significant association between FMD and EPC (p = 0.66). FMD was significantly associated with hsCRP (p = 0.002) and leptin (p = 0.003), but the EPC were not. Neither FMD nor EPC were significantly associated with uterine artery blood flow.
  
  
  CONCLUSIONS
  Changes in FMD were significantly associated with inflammatory biomarkers, suggesting that the reduced nitric oxide-dependent vasodilatation in late gestation is related to maternal inflammatory response. As EPC and FMD did not correlate, mechanisms other than mobilization of EPC to repair endothelial damage must be responsible for the gestational-age-associated increase in EPC.
authors.affiliation: Women's Health and Perinatology Research Group, Department of Clinical Medicine, Faculty of Health Sciences, UiT- The Arctic University of Norway, Tromsø, Norway.|Department of Obstetrics and Gynecology, University Hospital of North Norway, Tromsø, Norway.
authors.forename: Kari
authors.identifier: http://orcid.org/0000-0003-2276-1508
authors.initials: K
authors.lastname: Flo
authors.affiliation: Department of Oncology, University Hospital of North Norway, Tromsø, Norway.|Immunology research group, Department of Medical Biology, UiT- The Arctic University of Norway, Tromsø, Norway.
authors.forename: Egil S
authors.identifier: http://orcid.org/0000-0001-7372-6767
authors.initials: ES
authors.lastname: Blix
authors.affiliation: Immunology research group, Department of Medical Biology, UiT- The Arctic University of Norway, Tromsø, Norway.
authors.forename: Anne
authors.identifier: http://orcid.org/0000-0002-3802-4986
authors.initials: A
authors.lastname: Husebekk
authors.affiliation: Immunology research group, Department of Medical Biology, UiT- The Arctic University of Norway, Tromsø, Norway.
authors.forename: Anders
authors.identifier: http://orcid.org/0000-0001-9104-2377
authors.initials: A
authors.lastname: Thommessen
authors.affiliation: Immunology research group, Department of Medical Biology, UiT- The Arctic University of Norway, Tromsø, Norway.
authors.forename: Andreas T
authors.identifier: http://orcid.org/0000-0002-1633-1168
authors.initials: AT
authors.lastname: Uhre
authors.affiliation: Department of Community Medicine, Faculty of Health Sciences, UiT- The Arctic University of Norway, Tromsø, Norway.
authors.forename: Tom
authors.identifier: http://orcid.org/0000-0002-2709-9472
authors.initials: T
authors.lastname: Wilsgaard
authors.affiliation: Women's Health and Perinatology Research Group, Department of Clinical Medicine, Faculty of Health Sciences, UiT- The Arctic University of Norway, Tromsø, Norway.
authors.forename: Åse
authors.identifier: http://orcid.org/0000-0001-6923-9659
authors.initials: Å
authors.lastname: Vårtun
authors.affiliation: Women's Health and Perinatology Research Group, Department of Clinical Medicine, Faculty of Health Sciences, UiT- The Arctic University of Norway, Tromsø, Norway.|Department of Obstetrics and Gynecology, University Hospital of North Norway, Tromsø, Norway.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Acharya
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001916:Brachial Artery / Q000502:physiology*; D066026:Endothelial Progenitor Cells / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D008137:Longitudinal Studies; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D011446:Prospective Studies; D018608:Ultrasonography, Doppler; D055988:Uterine Artery / Q000000981:diagnostic imaging* / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology
chemical_list: D015415:Biomarkers
keywords: EPC; FMD; inflammation; pregnancy; uterine artery doppler