title: Roles of apolipoprotein E (ApoE) and inducible nitric oxide synthase (iNOS) in inflammation and apoptosis in preeclampsia pathogenesis and progression.
abstract: OBJECTIVE
  To investigate potential roles of inducible nitric oxide synthase (iNOS) and apolipoprotein (apoE) in inflammation and apoptosis promoting pathological changes in preeclampsia in pregnant mice with apoE and/or iNOS knock out.
  
  
  METHODS
  B6.129 mice were crossed to produce WT, apoE(-/-), apoE(+/-), iNOS(-/-), iNOS(+/-) and apoE(-/-)iNOS(-/-) groups. Variants were confirmed by PCR. Serum lipid parameters (triglycerides, TG; total cholesterol, TC; high density lipoprotein, HDL; and low density lipoprotein, LDL), NO levels and placental electronic microscopic ultrastructures were evaluated, and blood pressure (BP), 24-hour urine protein and pregnancy outcomes were recorded for pregnant F1 generation mice. Placental expressions of inflammatory (tumor necrosis factor-α, TNF-α; interleukin-6, IL-6; nuclear factor-κB, NF-κb) and apoptotic markers (Bcl-2 associated X protein, Bax, B-cell lymphoma/leukemia-2, Bcl-2, and Caspase-3) were evaluated via Western blot.
  
  
  RESULTS
  Serum lipids, BP and 24-hour urine protein levels were shown to be significantly higher and parturition and placenta weights were lower in apoE(-/-) and apoE(-/-)iNOS(-/-) groups (p<0.05). NO levels were lower in the apoE(-/-)iNOS(-/-) group. In addition, inflammatory/apoptosis parameters, including TNF-α, IL-6, NF-κb, Bax, Bcl-2 and Caspase-3 in the apoE(-/-)iNOS(-/-) group (p<0.01), as well as in the apoE(-/-) group (p<0.05), and NF-κB, Bax in iNOS(-/-) group (p<0.05) were higher compared with WT group. However, most of the inflammatory/apoptosis parameters in the iNOS(+/-) and the apoE(+/-) groups (p>0.05) showed no differences. In addition, placenta vascular endothelial and trophoblast cell morphological changes were demonstrated in both the apoE(-/-)iNOS(-/-) and apoE(-/-) groups.
  
  
  CONCLUSIONS
  Elevated lipid metabolism and inflammatory/apoptosis parameters suggest a potentially significant role of apoE in preeclampsia pathology, as well as a relationship between iNOS and preeclampsia progression.
authors.affiliation: Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.
authors.forename: Luyi
authors.initials: L
authors.lastname: Mao
authors.forename: Qiongjie
authors.initials: Q
authors.lastname: Zhou
authors.forename: Shufeng
authors.initials: S
authors.lastname: Zhou
authors.forename: Rhonda R
authors.initials: RR
authors.lastname: Wilbur
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism*; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure; D018450:Disease Progression; D005260:Female; D005838:Genotype; D007249:Inflammation; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism; D011225:Pre-Eclampsia / Q000201:enzymology* / Q000473:pathology*; D011247:Pregnancy
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D008055:Lipids; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse