title: Microvascular permeability is related to circulating levels of tumour necrosis factor-alpha in pre-eclampsia.
abstract: BACKGROUND
  The mechanism for the increased microvascular permeability which, underline many of the complications of pre-eclampsia, remain unexplained. It has been suggested that a factor present in the maternal circulation in pregnancies complicated by the disease may be responsible for increased microvascular permeability. In this study, we have investigated the relationship between filtration capacity (K(f)), an index of microvascular permeability, and maternal levels of VEGF, leptin and TNF-alpha, all of which are known permeability factors whose plasma levels are increased in pre-eclampsia.
  
  
  METHODS
  We used a small cumulative pressure step venous congestion plethysmography protocol to compare K(f), an index of microvascular permeability, during the third trimester of 20 women with pre-eclampsia, 18 normal pregnant women and 18 non-pregnant female matched controls. Blood samples were obtained to measure plasma levels of VEGF, leptin, TNF-alpha plasma protein concentrations and full blood count.
  
  
  RESULTS
  Microvascular filtration capacity (K(f)) was significantly increased in pre-eclampsia compared to the other groups (P<<0.0001, ANOVA). K(f) was also increased in the normal pregnant group when compared to the non-pregnant controls (P=0.02). Plasma levels of VEGF, leptin and TNF-alpha were significantly greater in pre-eclampsia compared to normal pregnancy and non-pregnant controls (P<0.0001, ANOVA, for all three analyses). Total plasma protein and albumin concentrations were significantly lower in the normal pregnant and pre-eclamptic groups, compared to the non-pregnant controls (P<0.0001, ANOVA). K(f) was significantly related to TNF-alpha in pre-eclampsia (r=0.53, P=0.018), and with VEGF in the non-pregnant controls (r=0.6, P=0.02). No significant relationship was observed between K(f) and VEGF, leptin and TNF-alpha during normal pregnancy. There was a significant inverse correlation between plasma albumin concentration and filtration capacity in the normal pregnant (r=-0.94, P<0.0001) and non-pregnant (r=-0.87, P<0.0001) groups but not in the women with pre-eclampsia (r=-0.18, P=0.8).
  
  
  CONCLUSIONS
  These data show that that microvascular filtration capacity is significantly increased in pre-eclampsia, and correlates with circulating levels of TNF-alpha but not leptin or VEGF.
authors.affiliation: Department of Maternal and Fetal Medicine, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Chelsea and Westminster Hospital, London, UK. n.anim@ic.ac.uk
authors.forename: Nick
authors.initials: N
authors.lastname: Anim-Nyame
authors.forename: John
authors.initials: J
authors.lastname: Gamble
authors.forename: Suren R
authors.initials: SR
authors.lastname: Sooranna
authors.forename: Mark R
authors.initials: MR
authors.lastname: Johnson
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Steer
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D002199:Capillary Permeability; D016228:Endothelial Growth Factors / Q000097:blood; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D020738:Leptin / Q000097:blood; D008222:Lymphokines / Q000097:blood; D010991:Plethysmography; D011225:Pre-Eclampsia / Q000097:blood* / Q000378:metabolism; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*; D014527:Uric Acid / Q000097:blood; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D008222:Lymphokines; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014527:Uric Acid