[show abstract][hide abstract] ABSTRACT: Preeclampsia is a hypertensive disorder unique to pregnancy. Although the pathogenesis of the disease begins with aberrant spiral artery invasion in the first trimester, clinical symptoms usually do not present until late in pregnancy. Apolipoprotein CII (ApoCII) and its negative regulator, apolipoprotein CIII (ApoCIII), have recently been described as atherogenesis biomarkers in models of cardiovascular disease. Given the similarities in pathology, etiology, and clinical presentation between cardiovascular disease and preeclampsia, we hypothesized that the ratio of ApoCIII to ApoCII in maternal first trimester plasma would predict preeclampsia later in pregnancy. To test this hypothesis, plasma was prospectively collected from 311 nulliparas at 8 to 12 weeks gestation. After delivery, patients were divided into cohorts based on preeclampsia diagnosis. Conditioning monocytes with preeclamptic plasma potentiated monocyte adhesion to endothelial cells in an in vitro model. The ratio of ApoCIII to ApoCII was significantly elevated in patients with severe preeclampsia relative to normotensive and gestational hypertensive individuals (P < .05) as determined by mass spectrometry and competitive enzyme-linked immunosorbent assay (ELISA) assays. These results support a predictive change in the ratio of ApoCIII to ApoCII in pregnancies complicated by severe preeclampsia.
[show abstract][hide abstract] ABSTRACT: The purpose of this study was to characterize effect of progesterone (P4) on interleukin-6 (IL-6) production by fetoplacental artery explants, fetal granulocytes, and fetal and maternal mononuclear cells.
Arteries and cord blood were obtained from 5 term pregnancies undergoing repeat cesarean section. Maternal blood was obtained from another 6 women at 16 to 20 weeks' gestation. Tissues were fractionated by dissection or Histopaque gradient. Specimens were incubated in physiologic media then exposed to lipopolysaccharide (LPS) or P4 alone, or pretreated with P4 and then exposed to LPS. Samples were evaluated for IL-6 by enzyme-linked immunosorbent assay (ELISA).
Arteries and fetal and maternal mononuclear cells exposed to LPS increased IL-6 secretion by 9-, 27-, and 29-fold, respectively. P4 pretreatment blocked LPS induction of IL-6. Fetal granulocytes did not increase IL-6 production in response to LPS exposure.
LPS induces IL-6 in arteries and fetal and maternal mononuclear cells. P4 pretreatment significantly blocks this effect in these cell populations, suggesting possible targets for anti-inflammatory actions of P4 in prevention of preterm birth.
American journal of obstetrics and gynecology 11/2006; 195(4):1015-9. · 3.28 Impact Factor
[show abstract][hide abstract] ABSTRACT: This study was undertaken to determine whether 17-hydroxyprogesterone caproate (17P) has a vasoactive effect on fetoplacental vasculature.
Two cotyledons were obtained from each of 5 placentas. Baseline perfusion was established with Hanks-based solution. One cotyledon from each pair was then infused with perfusate to which U46619 a thromboxane sympathomimetic had been added. After 30 minutes, a dose of 17P was then administered to each cotyledon. Finally, a vasoconstricting dose of angiotensin II was administered to each cotyledon. Perfusion pressures were recorded throughout. Statistical analysis of pressure change for a single cotyledon was performed by using a paired t test. Statistical analysis of mean perfusion pressure difference between U46619 exposed and nonexposed cotyledons was analyzed by using a students t test.
17P did not significantly alter the perfusion pressure of the control cotyledon. (30.6 +/- 8.3 mm Hg vs 30.1 +/- 7.8 mm Hg P = .48). 17P administration significantly lowered the perfusion pressure of the U46619 preconstricted vessels in comparison with preadministration. (60.1 +/- 13 mm Hg vs 27.3 +/- 7.1 mm Hg P = .03). Both groups of cotyledons responded with vasoconstriction to angiotension II with no difference in response between groups (38.3 +/- 12 mm Hg vs 45.8 +/- 8.2 mm Hg P = .63).
17P reverses induced vasoconstriction by U46619 in fetoplacental arteries.
American journal of obstetrics and gynecology 11/2006; 195(4):1011-4. · 3.28 Impact Factor
[show abstract][hide abstract] ABSTRACT: The purpose of this study was to determine if progesterone has an effect on fetoplacental artery production of inflammatory cytokines.
Chorionic plate arteries were dissected from 5 placentas obtained from normal pregnancies after delivery at term. Arteries were incubated in Dulbecco's modified Eagle's medium (DMEM) alone, DMEM and lipopolysaccharide (LPS), DMEM with progesterone (P4), and DMEM with P4 and LPS. Samples of the tissue culture media were collected and evaluated for interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interleukin-10 (IL-10) by immunoassay.
There was a significant decrease in the production of IL-6 in P4-exposed fetoplacental arteries after LPS stimulation (P < .001). IL-10 and TNF-alpha levels were similar in control and treatment groups after LPS exposure.
Pretreating fetoplacental arteries with P4 significantly decreased the production of IL-6 after LPS stimulation without altering the production of TNF-alpha or IL-10.
American Journal of Obstetrics and Gynecology 10/2005; 193(3 Pt 2):1144-8. · 3.88 Impact Factor