title: PP010. Alpha-1-microglobulin protects from heme induced placenta and kidney damage in a pregnant ewe model for preeclampsia.
abstract: BACKGROUND
  Previous gene expression analysis have identified fetal hemoglobin (HbF) as a plausible etiological factor in preeclampsia. Free hemoglobin and its degradation products, e.g. heme, are known to cause oxidative stress, tissue damage, and vaso-constriction, typical findings in preeclampsia.
  
  
  OBJECTIVE
  To study alpha-1-microglobulin (A1M), an endogenous radical scavenger and heme-binder, as a potential treatment for preeclampsia using the pregnant ewe preeclampsia model. Free Hb and heme are known to take part in the pathology of this model and therefor well suited for evaluation of recombinant A1M as a therapy.
  
  
  METHODS
  11 pregnant ewes, at gestational age 125-131 days, were acclimatized for 36h and then starved for another 36h to induce preeclampsia symptoms. At the end of starvation period, they were treated either with placebo (n=6) or A1M injections (n=5). After injections, food was re-introduced and ewes further followed for 72h. The ewes were sacrificed the 6th day after beginning of acclimatization. Throughout the 6 days, the animals were monitored for blood pressure and different blood and urine parameters. Whole blood, kidney and placenta tissue samples were collected from the ewes. Gene expression analysis, blood analysis, histology and electron microscopy were used to evaluate the therapeutic effects of A1M.
  
  
  RESULTS
  Starvation increased the amount of free heme in the blood. The ultrastructure of the placenta and kidney were damaged in a way similar to what previously have been described for PE. The glomeruli and the tubuli were damaged which was reflected by increased Ficol clearance and increased plasma creatinine levels. Treatment with A1M significantly normalized the kidney functions. The most profound changes on gene expression level were found in white blood cells in the starved animals. Starvation decreases mRNA expression for anti-oxidants such as CAT (P=0.04), SOD1 (P=0.008), SOD2 (1.8-fold) as well as angiogenetic factors such as VEGF (P=0.02) and HGF (1.6-fold). A1M treatment rescued the decreased expression of SOD2 (P=0.04) and HGF (2-fold).
  
  
  CONCLUSIONS
  A1M is well tolerated and shows high potential as a treatment for PE-like symptoms in the pregnant ewe model for PE.
authors.forename: Anneli
authors.initials: A
authors.lastname: Edström-Hägerwall
authors.forename: Stefan
authors.initials: S
authors.lastname: Hansson
authors.forename: Vera
authors.initials: V
authors.lastname: Casslén
authors.forename: Lena
authors.initials: L
authors.lastname: Rosenlöf
authors.forename: Josefin
authors.initials: J
authors.lastname: Axelsson
authors.forename: Bengt
authors.initials: B
authors.lastname: Rippe
authors.forename: Karel
authors.initials: K
authors.lastname: Marsal
authors.forename: Matthias
authors.initials: M
authors.lastname: Mörgelin
authors.forename: Bo
authors.initials: B
authors.lastname: Åkerström
authors.forename: Magnus
authors.initials: M
authors.lastname: Gram