title: [Study on p38 mitogen activated protein kinase in vascular endothelial cells dysfunction in preeclampsia].
abstract: OBJECTIVE
  To study expression and activation of p38 mitogen activated protein kinase (MAPK) in vascular endothelial cells dysfunction in preeclampsia.
  
  
  METHODS
  From Sept. 2009 to Mar. 2010, 54 pregnant women underwent deliveries in the First Affiliated Hospital of Chongqing Medical University were enrolled in this study, including 20 patients in mild preeclampsia group, 16 patients in severe preeclampsia group and 18 women with term cesarean section without perinatal complications as control group. Placental endothelial cells were labeled by CD₃₄ to assay microvessel density (MVD) of each group. Immunohistochemical SP and western blot were used to detect localization and expression of p-p38 MAPK protein, respectively. The levels of sera soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng) were measured by ELISA.
  
  
  RESULTS
  (1) The MVD of placenta were 103 ± 3 in control group, 81 ± 5 in mild preeclampsia group and 63 ± 4 in severe group, respectively, which showed statistical difference among each group (P < 0.05). (2) The expression of p38 MAPK protein were 0.84 ± 0.05 in control group, 0.90 ± 0.14 in mild group and 0.86 ± 0.18 in severe group, which did not reach remarkable difference among each group (P > 0.05). The expression of p-p38 MAPK protein were 0.13 ± 0.05 in control group, 0.59 ± 0.12 in mild group and 1.16 ± 0.18 in severe group, which show statistical difference among each group (P < 0.05). (3) The localization of p-p38 was in trophoblast, endothelial cells and a few stromal cells in placenta. (4) The level of sFlt-1 and sEng: (1) The concentration of sFlt-1 and sEng were (5.2 ± 0.3) and (10.9 ± 0.4) µg/L in control group, (12.5 ± 1.2) and (20.4 ± 5.3) µg/L in mild group and (19.3 ± 3.0) and (29.5 ± 3.7) µg/L in severe group. When drawing paired comparison in those groups, the differences showed statistical difference (P < 0.05). (2) There were positive correlations between p-p38 MAPK protein levels and the concentrations of serum sFlt-1, sEng in preeclampsia groups (r = 0.68, P < 0.05; r = 0.87, P < 0.05).
  
  
  CONCLUSIONS
  The remarkable activation of the p38 MAPK in the placenta of patients with preeclampsia induced the increased levels of sFlt-l and sEng in maternal serum, which confer the injury of vascular endothelial cells that caused the significant decline of MVD in placentas. p38 MAPK signaling might be one of the key pathways in vascular endothelial cell dysfunction in preeclampsia.
authors.affiliation: Department of Obstetrics and Gynecology, First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Luo
authors.forename: Dan-dan
authors.initials: DD
authors.lastname: Liu
authors.forename: Hong-bo
authors.initials: HB
authors.lastname: Qi
authors.forename: Zhen-wei
authors.initials: ZW
authors.lastname: Yao
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000097:blood*; D016022:Case-Control Studies; D000071063:Endoglin; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D055806:Microvessels / Q000473:pathology; D010766:Phosphorylation; D010920:Placenta / Q000098:blood supply / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000097:blood / Q000201:enzymology / Q000378:metabolism*; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000097:blood*; D012720:Severity of Illness Index; D015398:Signal Transduction; D014327:Trophoblasts / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D011956:Receptors, Cell Surface; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D048051:p38 Mitogen-Activated Protein Kinases