title: [The changes of LCHAD in preeclampsia with different clinical features and the correlation with NADPH P47-phox, p38MAPK-α, COX-2 and serum FFA and TG].
abstract: OBJECTIVE
  To investigate the changes of fatty acid oxidase in the placenta of preeclampsia cases with different clinical features, and the relationship with oxidative stress and inflammatory response. To study the correlation of serum free fatty acid (FFA) and triglycerides (TG) level in early second trimester with the molecular changes of the long-chain fatty acid oxidase in the third trimester.
  
  
  METHODS
  This was prospective cohort study, in which cases with singleton pregnancies who archived in Haidian Maternal and Children's Hospital, Beijing, from January 1st 2012 to May 31st, with regular prenatal care were included. Doppler ultrasound was used for screening for the presence of early diastolic notch of uterine artery at 22-24 weeks of gestation. All the 101 cases with the early diastolic notch of uterine artery were included as the notch group, and 377 cases without the early diastolic notch of uterine artery were included as the non-notch group. The perinatal outcomes and the incidence of hypertensive disorders in pregnancy of the two groups were observed. The serum level of FFA and TG was tested, and the mRNA and protein expression of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD), P47-phox subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, p38 mitogen-activated protein kinase a (p38MAPK-α) and cyclooxygenase-2 (COX-2) were detected using real-time quantitative PCR and western blot. The relationship between serum level of FFA and TG and the mRNA and protein expression of LCHAD, NADPH P47-phox, p38MAPK-α and COX-2 of the placental tissue specimens were analyzed.
  
  
  RESULTS
  (1) In the notch group, there were 9 cases of early-onset preeclampsia, 15 cases of late-onset preeclampsia and 10 cases of gestational hypertension;and there were 8 cases of late-onset preeclampsia and 18 cases of gestational hypertension in the non-notch group. 15 cases with normal blood pressure in each group were randomly selected as the control group. (2)The serum level of TG of cases of early-onset preeclampsia, late-onset preeclampsia and gestational hypertension in the notch group were (2.0 ± 0.8), (1.8 ± 0.6)and (1.9 ± 0.7)mmol/L, and that of FFA were(0.68 ± 0.26), (0.52 ± 0.10) and (0.52 ± 0.17)mmol/L, respectively. The serum level of TG of cases of late-onset preeclampsia and gestational hypertension in the non-notch group were (1.6 ± 0.6) and (1.4 ± 0.4)mmol/L, and that of FFA were (0.49 ± 0.11) and (0.48 ± 0.05)mmol/L, respectively. The serum level of TG and FFA in the control group were (1.4 ± 0.5) and (0.52 ± 0.06)mmol/L, respectively. The TG level of the notch group was higher than that of the control group, and the difference was statistically significant (P < 0.05). The FFA level of the early-onset preeclampsia in the notch group was higher than that of late-onset preeclampsia in the notch group, late-onset preeclampsia in the non-notch group and the control group, and the difference was statistically significant (P < 0.05). (3) The mRNA expression of LCHAD in the placenta of early-onset preeclampsia in the notch group was significantly lower than that of the late-onset preeclampsia in the notch group, late-onset preeclampsia in the non-notch group and the control group (P < 0.01). The mRNA expression of NADPH P47-phox of the early-onset preeclampsia in the notch group were significantly higher than that of late-onset preeclampsia in the notch group, late-onset preeclampsia in the non-notch group and the control group (P < 0.01). The mRNA expression of p38MAPK-α of the early-onset preeclampsia in the notch group were significantly higher than that of late-onset preeclampsia in the notch group, late-onset preeclampsia in the non-notch group and the control group (P < 0.01). The mRNA expression of COX-2 of the early-onset preeclampsia in the notch group were significantly higher than that of late-onset preeclampsia in the notch group, late-onset preeclampsia in the non-notch group and the control group (P < 0.01). (4)The protein expression of LCHAD in the placenta of early-onset preeclampsia in the notch group, late-onset preeclampsia in the notch group and gestational hypertension in the notch group were significantly lower than that of the control group (P < 0.01); and the protein expression of LCHAD in the placenta of early-onset preeclampsia in the notch group was significantly lower than that of late-onset preeclampsia in the non-notch group (P < 0.01). The protein expression of NADPH P47-phox in the placenta of early-onset preeclampsia in the notch group was significantly higher than that of late-onset preeclampsia in the non-notch group and control group (P < 0.05). The protein expression of p38MAPK-α in the placenta of early-onset preeclampsia in the notch group was significantly higher than that of late-onset preeclampsia in the notch group, late-onset preeclampsia in the non-notch group and control group (P < 0.01). The protein expression of COX-2 in the placenta of early-onset preeclampsia in the notch group, late-onset preeclampsia in the notch group, gestational hypertension in the notch group, late-onset preeclampsia in the non-notch group, and gestational hypertension in the non-notch group, were significantly higher than that of control group (P < 0.01). (5)The blood concentration of maternal FFA in the early-onset preeclampsia in the notch group was significantly negatively correlated with the mRNA and protein expression of placental LCHAD (r = -0.810, -0.932, P < 0.01). There was no correlation between maternal TG level and the mRNA and protein expression of placental LCHAD in each group(P > 0.05). (6)The mRNA expression of placental LCHAD in the early-onset preeclampsia in the notch group was significantly negatively correlated with the mRNA expression of placental NADPH P47-phox and COX-2 (r = - 0.877, -0.762, P < 0.05). The mRNA expression of placental LCHAD in the control group was significantly negatively correlated with the mRNA expression of placental COX-2 (r = -0.565, P < 0.01). The protein expression of placental LCHAD in the early-onset preeclampsia in the notch group was significantly negatively correlated with the protein expression of NADPH P47-phox (r = -0.818, P < 0.01). The protein expression of placental LCHAD in the control group was significantly negatively correlated with the protein expression of COX-2 (r = -0.502, P < 0.01).
  
  
  CONCLUSIONS
  The placental mRNA and protein expression of long-chain fatty acid oxidation enzymes were different in different clinical features of preeclampsia, which were reduced more obviously in the early-onset preeclampsia in the notch group than that of the late-onset preeclampsia in the notch group, and were negatively correlated with the elevated serum FFA level, significantly enhanced oxidative stress and inflammatory response, but with no correlation with serum TG level.
authors: Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.
authors: Fengqiu
authors: F
authors: Li
authors: Email: zi_yang@email.com.
authors: Zi
authors: Z
authors: Yang
authors: Aiqing
authors: A
authors: Zhang
authors: Xiaole
authors: X
authors: Sun
authors: Jialüe
authors: J
authors: Wang
authors: Ran
authors: R
authors: Meng
mesh_terms: D005260:Female; D006801:Humans; D011247:Pregnancy; D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000172:deficiency; D009202:Cardiomyopathies; D015331:Cohort Studies; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005227:Fatty Acids / Q000097:blood; D006973:Hypertension; D008052:Lipid Metabolism, Inborn Errors; D017240:Mitochondrial Myopathies; D063991:Mitochondrial Trifunctional Protein / Q000172:deficiency; D009249:NADP / Q000378:metabolism; D019255:NADPH Oxidases; D009422:Nervous System Diseases; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D011225:Pre-Eclampsia / Q000378:metabolism; D011263:Pregnancy Trimester, Third / Q000378:metabolism; D011446:Prospective Studies; D012206:Rhabdomyolysis; D012333:RNA, Messenger; D014280:Triglycerides / Q000097:blood
chemical_list: D015094:3-Hydroxyacyl CoA Dehydrogenases; D051546:Cyclooxygenase 2; D005227:Fatty Acids; D063991:Mitochondrial Trifunctional Protein; D009249:NADP; D019255:NADPH Oxidases; D048051:p38 Mitogen-Activated Protein Kinases; D012333:RNA, Messenger; D014280:Triglycerides