Adipocytokine expression in placentas from pre-eclamptic and chronic hypertensive patients.

OBJECTIVE: Growing evidence suggests that concentration of the adipocytokines leptin and adiponectin may be affected by risk of hypertension during pregnancy. Leptin and leptin receptor gene expression has been studied in placentas obtained from pre-eclamptic patients, but not in those with chronic high blood pressure (CHBP). Adiponectin receptors remain unstudied in placentas obtained from hypertensive patients. METHODS: Therefore, we investigated relative mRNA expression of selected adipocytokine genes (leptin, leptin receptors (LEPRA, LEPRB, LEPRC, LEPRD) and adiponectin receptors (ADIPOR1, ADIPOR2)) in placental tissues from women with pre-eclampsia (n = 6) or CHBP (n = 8). Placentas from 28 normotensive patients were analyzed as controls. mRNA extracted from biopsies taken from the maternal and fetal sides of the placenta was investigated using real-time polymerase chain reaction. RESULTS: Compared with controls, significant increases in leptin mRNA expression were seen in placentas from pre-eclamptic patients on the maternal (p = 0.01) and fetal (p = 0.02) sides, and in placentas from CHBP mothers on the fetal side (p = 0.001). Maternal-side tissue from CHBP patients was not significantly different from that of controls (p = 0.08), but this might be due to the small sample size. No significant differences were seen in mRNA expression for most of the adipocytokine receptors tested for hypertensive cases compared with controls. However, there was a decrease in LEPRC (pre-eclamptic, maternal side, p = 0.03) and LEPRD (pre-eclamptic, maternal side, p = 0.01; CHBP, fetal side, p = 0.009) in case-control analysis. CONCLUSIONS: This pilot study shows that increases seen in leptin expression in placentas from hypertensive mothers might be a consequence of defects in placentation associated with this disease, and motivates further region-specific adipocytokine gene expression analysis across this organ.

Elevated soluble vascular cell adhesion molecule-1, elevated Homocyst(e)inemia, and hypertriglyceridemia in relation to preeclampsia risk.

BACKGROUND: We examined the relationship of maternal plasma concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1), a specific marker of endothelial dysfunction, and risk of preeclampsia. We also evaluated the relationship in the presence and absence of maternal hypertriglyceridemia and hyperhomocystein(e)mia. METHODS: A total of 170 women with preeclampsia and 184 control subjects were included in this case-control study analysis. Maternal postdiagnosis plasma sVCAM-1 concentrations were determined using immunoassays. Total plasma homocysteine (tHcy) was measured using high-performance liquid chromatography with electrochemical detection procedures; and triglyceride concentrations were determined using standard enzymatic procedures. Logistic regression procedures were used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for confounders. RESULTS: The relative risk of preeclampsia (as estimated by the OR) was increased 3.6-fold for women with sVCAM-1 concentrations >/=842 ng/mL compared with women who had lower concentrations (OR = 3.6; 95% CI 1.8 to 7.4). Of the three biological markers investigated, elevated sVCAM-1 concentrations was most strongly related to preeclampsia risk (OR = 4.6, 95% CI 1.6 to 13.5), followed by hyperhomocysten(e)mia (OR = 2.4, 95% CI 0.8 to 7.4) and hypertriglyceridemia (OR = 2.1, 95% CI 0.9 to 5.0). Compared with women who did not have any of the three risk factors, those with all three risk factors had an extremely high risk of preeclampsia (OR = 26.4; 95% CI 8.5 to 81.9). CONCLUSIONS: These findings suggest that elevated sVCAM-1 concentrations are associated with an increased risk of preeclampsia. Our findings extend the literature by documenting progressively increased risk with increasing numbers of biological markers of dyslipidemia and endothelial dysfunction.

A case-control study of oxidized low density lipoproteins and preeclampsia risk.

Diffuse vascular endothelial dysfunction, secondary to oxidative stress, is an important pathological feature of preeclampsia. Oxidative conversion of low density lipoproteins (LDL) to oxidized-LDL (Ox-LDL) is considered an important step in transforming macrophages into lipid-laden foam cells destined to develop into early atherosclerotic-like lesions. In our study of 95 women with preeclampsia and 100 controls, we evaluated the association between maternal plasma Ox-LDL concentrations and preeclampsia risk. Ox-LDL concentrations were measured using a solid phase two-site enzyme immunoassay. Plasma lipids were measured using standard enzymatic procedures. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for confounders. Plasma Ox-LDL concentrations were positively correlated with cholesterol, triglyceride (TG), and LDL concentrations in cases and controls, (Spearman's r ranging from 0.39-0.48, p-values all <0.01). There was no evidence of an increased risk of preeclampsia across increasing quartiles of Ox-LDL. The ORs for successive quartiles, with the lowest as the reference group, were as follows: 1.0, 1.1, 0.6, and 1.2. Women with extremely high concentrations of Ox-LDL (> or =73 U/L, the upper decile), as compared with those with lower values (<73 U/L) had a 2.7-fold increased risk of preeclampsia (95% CI 1.0-6.8). Women with high Ox-LDL and high TG concentrations (> or =284 mg/dl), as compared with those without these two factors, had a 9.6-fold increased preeclampsia risk (95% CI 2.0-45.6). Elevated Ox-LDL, particularly in conjunction with elevated TG, appears to be a risk factor of preeclampsia.

Hepatic lipase gene polymorphism, pre-pregnancy overweight status and risk of preeclampsia among Peruvian women.

We examined the association between the hepatic lipase (LIPC) gene promoter polymorphism (-514C/T) and risk of preeclampsia among Peruvian women. We also evaluated whether this association is modified by maternal pre-pregnancy overweight status. Using a case control study design, 157 preeclampsia cases and 180 normotensive controls were enrolled in the study. Genotyping was conducted using PCR amplification, NlaIII enzyme digestion and gel electrophoresis. Logistic regression procedures were used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CI). After adjusting for confounding by maternal age, parity and pre-pregnancy body mass index (BMI), the relative risks of preeclampsia for women with LIPC -514CT and LIPC -514TT genotypes were 1.0 (95% CI 0.5-2.2) and 1.5 (95% CI 0.7-3.3) respectively, using women with LIPC -514CC genotype as a reference. Women who were both overweight and who had the LIPC -514TT genotype had a significant 3-fold increased risk of preeclampsia (Adj. OR:3.0 95% CI 1.3-6.8) as compared to those women who were not overweight and had the LIPC -514CC/CT genotype. In this study, we found that LIPC -514TT genotype and overweight status, when occurring together, were associated with a 3-fold increase in risk of preeclampsia among Peruvian women.

Maternal plasma concentrations of insulinlike growth factor-1 and insulinlike growth factor-binding protein-1 in early pregnancy and subsequent risk of preeclampsia.

OBJECTIVES: We investigated the relationship between maternal plasma free insulinlike growth factor-1 (IGF-1) and insulinlike growth factor-binding protein-1 (IGFBP-1) concentrations and risk of preeclampsia. DESIGN AND METHODS: Maternal blood samples were collected at 13 weeks' gestation on average. From the cohort, we selected 53 women who developed preeclampsia and 477 who remained normotensive. Free IGF-1 and IGFBP-1 concentrations were measured using immunoassays. Logistic regression procedures were used to calculate odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: Women who developed preeclampsia had 18% and 27% lower concentrations of free IGF-1 and IGFBP-1, respectively, than controls (P < 0.05). There was a 57% reduced risk of preeclampsia among women with free IGF-1 concentrations of >or= 0.81 ng/mL (OR = 0.43, 95% CI 0.23-0.83) and a 43% reduced risk among women with IGFBP-1 concentrations of >or= 72.36 ng/mL (OR = 0.53, 95% CI 0.23-1.21). CONCLUSIONS: Alterations of free IGF-1 and IGFBP-1 concentrations in maternal plasma during early pregnancy are associated with risk of preeclampsia. These associations may help to further elucidate the pathologic processes of preeclampsia.

Hyperhomocyst(e)inemia and elevated soluble vascular cell adhesion molecule-1 concentrations are associated with an increased risk of preeclampsia.

Hyperhomocyst(e)inemia (HHcy) is a risk factor of endothelial dysfunction and preeclampsia. Soluble vascular cell adhesion molecule-1 (sVCAM-1), a specific marker of endothelial dysfunction, is elevated in preeclampsia. Few have assessed the joint contribution of these biomarkers in predicting preeclampsia. We assessed the extent to which HHcy and elevated sVCAM-1 are independently and jointly associated with preeclampsia. We conducted a case-control analysis of 100 preeclampsia cases and 100 controls to test our study hypothesis. Maternal plasma was collected before labor onset. Total plasma homocysteine (tHcy) was measured using high-performance liquid chromatography with electrochemical detection procedures. Plasma sVCAM-1 was determined using ELISA. Using the distribution of each analyte among controls, elevated tHcy was defined as plasma tHcy >6.6 micromol/l and elevated sVCAM-1 was defined as plasma concentrations >845 ng/ml (i.e., values above the median). Odds ratios (OR) and 95% confidence intervals (CIs) were calculated. Compared with women without elevated tHcy and without elevated sVCAM-1 (the referent group), those with elevated sVCAM-1 alone had a 4.1-fold increased risk of preeclampsia (95% CI 1.2-13.8). The OR for women with elevated tHcy alone was 2.2 (95% CI 0.6-7.9). The OR for women with elevated tHcy and sVCAM-1 was 13.2 (95% CI 4.1-42.2). Elevated tHcy and sVCAM-1 together were strongly associated with an increased risk of preeclampsia. Larger, prospective studies are needed to confirm these findings and to determine the extent to which elevated tHcy and sVCAM-1 together in early pregnancy are predictive of preeclampsia risk.

Plasma adiponectin concentrations in early pregnancy and subsequent risk of gestational diabetes mellitus.

Low plasma adiponectin has been identified as a risk factor for type 2 diabetes. Our objective was to determine the extent to which low maternal plasma adiponectin is predictive of gestational diabetes mellitus (GDM), a condition that is biochemically and epidemiologically similar to type 2 diabetes. We used a prospective, nested case-control study design to compare maternal plasma adiponectin concentrations in 41 cases with 70 controls. Subjects were selected from a population of 968 women who provided blood samples in early pregnancy. Plasma adiponectin was determined using an ELISA. Adiponectin concentrations were statistically significantly lower in women with GDM than controls (4.4 vs. 8.1 micro g/ml, P < 0.001). Approximately 73% of women with GDM, compared with 33% of controls, had adiponectin concentrations less than 6.4 micro g/ml. After adjusting for confounding, women with adiponectin concentrations less than 6.4 micro g/ml experienced a 4.6-fold increased risk of GDM, as compared with those with higher concentrations (95% confidence interval, 1.8-11.6). Our findings are consistent with other reports suggesting an association between hypoadiponectemia and risk of type 2 diabetes. Our findings extend the literature to include GDM. Studies designed to examine the effect of dietary and pharmacological mediators of adiponectin concentrations in pregnant and nonpregnant subjects are warranted.

Transforming growth factor-beta1 (TGF-beta1) in plasma is associated with preeclampsia risk in Peruvian women with systemic inflammation.

BACKGROUND: In a case-control study of 100 preeclamptics and 100 controls, we assessed plasma transforming growth factor-beta1 (TGF-beta1) concentrations in relation to preeclampsia risk among Peruvian women with and without systemic inflammation. METHODS: Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The OR of preeclampsia increased across quartiles of TGF-beta1 concentrations. Women with elevated TGF-beta1 and a proinflammatory profile experienced the highest risk of preeclampsia (OR = 15.4, 95% CI 4.7-50.4). CONCLUSIONS: Our results confirm an association between TGF-beta1 and risk of preeclampsia and extend the literature by indicating a strong association in women with systemic inflammation.