Longitudinal serum concentrations of placental growth factor: Evidence for abnormal placental angiogenesis in pathologic pregnancies

Taylor, Robert N.; Grimwood, Jane; Taylor, Rennae S.; McMaster, Michael; Fisher, Susan J.; North, Robyn A.

doi:10.1067/mob.2003.111

Cited by 387 publications

(285 citation statements)

References 26 publications

Supporting

Mentioning

249

Contrasting

Unclassified

Order By: Relevance

“…In agreement with the existing literature on early pregnancy, [23][24][25][26][27] we found that low levels of PiGF at 10-15 weeks of gestation predict the subsequent development of pre-eclampsia. However, we found no significant link between sFlt-1 or sEng and pre-eclampsia during this gestational period, in keeping with the results from other authors.…”

Section: Discussionsupporting

confidence: 81%

The Interrelationship of Complement-Activation Fragments and Angiogenesis-related Factors in Early Pregnancy and Their Association With Preeclampsia

Lynch

Murphy

Gibbs

et al. 2011

Obstetric Anesthesia Digest

View full text Add to dashboard Cite

Objective-To determine the interrelationships during early pregnancy of complement-activation fragments Bb, C3a and sC5b-9, and angiogenesis-related factors placental growth factor (PiGF), soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), and their associations with pre-eclampsia. Design-Prospective cohort study. Setting-Denver complement study (June 2005-June 2008).Population-A total of 668 pregnant women with singleton gestations, recruited between 10 and 15 weeks of gestation.Methods-Using univariable and multivariable logistic regression analysis, concentrations of complement-activation fragments and angiogenesis-related factors were compared between 10 and Correspondence: Dr A Lynch, Department of Obstetrics and Gynecology, University of Colorado Denver School of Medicine, Mail Stop B198, 12631 East 17th Avenue, Aurora, CO 80045, USA. anne.lynch@ucdenver.edu. Disclosure of interestsThe authors have nothing to disclose. Contribution to authorshipAML designed and oversaw the study, conducted the data analysis, obtained the funding and wrote the manuscript; JRM provided statistical consultation; PCG provided consultation on the interpretation of complement results; RJL contributed his expertise in the area of angiogenesis-related factors; RSG contributed his expertise in maternal-fetal medicine. VMH and JES contributed their expertise in the area of complement research, and VMH served as mentor to AML on her NICHD K23 grant. Details of ethics approvalThe Colorado Multiple Institutional Review Board approved the study (COMIRB protocol number 07-0960). Interrelationships between these variables were tested using the non-parametric Spearman rank correlation coefficient. HHS Public AccessMain outcome measure-Pre-eclampsia. The association of complement-activation fragments and angiogenesis-related factors with obesity was also examined.Results-The mean (±SD) levels of complement Bb in early pregnancy among women who did and did not develop pre-eclampsia were 0.84 (±0.26) µg/ml and 0.69 (±0.2) µg/ml, respectively (P = 0.001). Concentrations of PiGF were significantly (P = 0.01) lower (31 ± 12 pg/ml) in early pregnancy in the pre-eclamptic group of women, as compared with the normotensive group (39 ± 32 pg/ml). The adjusted odds ratio (AOR) of Bb and PiGF were 2.1 (CI = 1.4-3.1, P < 0.0003) and 0.2 (CI = 0.07-0.7, P = 0.01), respectively. There was no significant difference in the levels of C3a, sC5b-9, sFlt-1 and sEng in early pregnancy among women who developed pre-eclampsia, compared with women who remained normotensive during pregnancy. Higher levels of Bb (P = 0.0001) and C3a (P = 0.03), and lower levels of sFlt-1 (P = 0.0002) and sEng (P = 0.0001) were found among women with obesity, compared with non-obese controls. No meaningful relationships were found between the complement-activation fragments and the angiogenesisrelated factors.Conclusions-In this cohort during early pregnancy, increased concentrations of complementactivation factor Bb and lower concentrations of PiGF were ...

show abstract

Section: Discussionsupporting

confidence: 81%

The Interrelationship of Complement-Activation Fragments and Angiogenesis-related Factors in Early Pregnancy and Their Association With Preeclampsia

Lynch

Murphy

Gibbs

et al. 2011

Obstetric Anesthesia Digest

View full text Add to dashboard Cite

show abstract

“…In humans, low levels of PlGF have been associated with pre-eclampsia (25)(26)(27)(28)(29)(30), and endometrial PlGF is reported to be an exclusive product of uNK cells in the late menstrual cycle. PlGF is also found in uNK cells from early, elective pregnancy terminations (5).…”

Section: Discussionmentioning

confidence: 99%

Genetic Deletion of Placenta Growth Factor in Mice Alters Uterine NK Cells

Tayade

Hilchie

et al. 2007

The Journal of Immunology

110

View full text Add to dashboard Cite

Placenta growth factor (PlGF; formerly PGF), a vascular endothelial growth factor gene family member, is expressed in human implantation sites by maternal uterine NK (uNK) and fetal trophoblast cells. Lower than normal concentrations of blood and urinary PlGF have been associated with impending onset of pre-eclampsia, a hypertensive disease of late human gestation characterized by limited intravascular trophoblast invasion. In pregnant rodents, delivery of the PlGF antagonist sFlt-1 or S-endoglin induces pre-eclampsia-like lesions. Mice genetically deleted in PlGF reproduce, but neither their implantation sites nor their uNK cell development are described. We combined real-time PCR of endometrium from nonpregnant and gestation day (gd)6–18 C57BL6/J (B6) mice with immunohistology to analyze PlGF expression in normal mouse pregnancy. To estimate the significance of uNK cell-derived PlGF, PlGF message was quantified in mesometrial decidua from pregnant alymphoid Rag2 null/common γ chain null mice and in laser capture-microdissected B6 uNK cells. Histopathologic consequences from PlGF deletion were also characterized in the implantation sites from PlGF null mice. In B6, decidual PlGF expression rose between gd8–16. uNK cells were among several types of cells transcribing PlGF in decidualized endometrium. Immature uNK cells, defined by their low numbers of cytoplasmic granules, were the uNK cells displaying the greatest number of transcripts. PlGF deletion promoted the early differentiation high numbers of binucleate uNK cells (gd8) but had no other significant, morphometrically detectable impact on implantation sites. Thus, in mice, PlGF plays an important role in successful uNK cell proliferation and/or differentiation.

show abstract

“…[16][17][18] Moreover, recent reports have indicated that the soluble form of the VEGF receptor-1 (sFlt-1) is increased in the placenta and serum of women with PE. [18][19][20][21] Thus, sFlt-1 may act by sequestering free PlGF and free VEGF, thereby preventing interaction between endothelial Median (interquartile range).…”

Section: Discussionmentioning

confidence: 99%

Different profiles of circulating angiogenic factors and adipocytokines between early‐ and late‐onset pre‐eclampsia

Masuyama

Segawa

Sumida

et al. 2010

BJOG

109

View full text Add to dashboard Cite

Objective Circulating angiogenic factors have been shown to be important in the pathophysiology of pre-eclampsia. Blood levels of adipocytokines differ in pre-eclampsia relative to controls and may also play an important role in disease pathogenesis. Differences in the circulating levels of these molecules were compared between matched normotensive controls and women with pre-eclampsia with onset before or at/after 32 weeks, and according to whether the women were of normal weight (18.5 < body mass index < 25) or overweight.Design A cross-sectional study of 110 pregnant Japanese women who visited the Department of Obstetrics and Gynecology, Okayama University Hospital, Okayama, Japan.Setting Tertiary referral centre serving 2000 births.Methods Serum concentrations of soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), soluble endoglin (sEng), adiponectin and leptin were measured in women with pre-eclampsia and in normotensive controls matched for age, gestational week, parity and body mass index.Main outcome measures Serum levels of sFlt-1, PlGF, the sFlt-1/ PlGF ratio, sEng, adiponectin and leptin.Results The sFlt-1/PlGF ratio in early-onset pre-eclampsia was significantly higher than that in late-onset pre-eclampsia (112.0 ± 30.2 versus 45.4 ± 43.8, P = 0.037). There was a significant elevation of leptin in both subtypes relative to controls (early: 58.6 ± 18.3 ng/ml versus 26.0 ± 6.7 ng/ml, P = 0.001; late: 39.5 ± 9.2 ng/ml versus 22.0 ± 4.3 ng/ml, P = 0.005), but adiponectin was increased only in late-onset pre-eclampsia (36.5 ± 13.4 lg/ml versus 12.0 ± 4.3 lg/ml, P = 0.003). Significant differences in angiogenic factors and adiponectin were found between normal and overweight women only in late-onset pre-eclampsia.Conclusions These data suggest that there are different profiles of angiogenic factors and adipocytokines between women who develop early-and late-onset pre-eclampsia.

show abstract

Longitudinal serum concentrations of placental growth factor: Evidence for abnormal placental angiogenesis in pathologic pregnancies

Cited by 387 publications

References 26 publications

The Interrelationship of Complement-Activation Fragments and Angiogenesis-related Factors in Early Pregnancy and Their Association With Preeclampsia

The Interrelationship of Complement-Activation Fragments and Angiogenesis-related Factors in Early Pregnancy and Their Association With Preeclampsia

Genetic Deletion of Placenta Growth Factor in Mice Alters Uterine NK Cells

Different profiles of circulating angiogenic factors and adipocytokines between early‐ and late‐onset pre‐eclampsia

Contact Info

Product

Resources

About