Cong Qian

Bio: Cong Qian is an academic researcher from National Institutes of Health. The author has contributed to research in topics: Preeclampsia & Pregnancy. The author has an hindex of 20, co-authored 31 publications receiving 6476 citations.

Circulating Angiogenic Factors and the Risk of Preeclampsia

Abstract: Background The cause of preeclampsia remains unclear. Limited data suggest that excess circulating soluble fms-like tyrosine kinase 1 (sFlt-1), which binds placental growth factor (PlGF) and vascul...

Soluble endoglin and other circulating antiangiogenic factors in preeclampsia.

Abstract: Background Alterations in circulating soluble fms-like tyrosine kinase 1 (sFlt1), an antiangiogenic protein, and placental growth factor (PlGF), a proangiogenic protein, appear to be involved in th...

Urinary placental growth factor and risk of preeclampsia.

Abstract: ContextPreeclampsia may be caused by an imbalance of angiogenic factors. We previously demonstrated that high serum levels of soluble fms-like tyrosine kinase 1 (sFlt1), an antiangiogenic protein, and low levels of placental growth factor (PlGF), a proangiogenic protein, predict subsequent development of preeclampsia. In the absence of glomerular disease leading to proteinuria, sFlt1 is too large a molecule to be filtered into the urine, while PlGF is readily filtered.ObjectiveTo test the hypothesis that urinary PlGF is reduced prior to onset of hypertension and proteinuria and that this reduction predicts preeclampsia.Design, Setting, and PatientsNested case-control study within the Calcium for Preeclampsia Prevention trial of healthy nulliparous women enrolled at 5 US university medical centers during 1992-1995. Each woman with preeclampsia was matched to 1 normotensive control by enrollment site, gestational age at collection of the first serum specimen, and sample storage time at −70°C. One hundred twenty pairs of women were randomly chosen for analysis of serum and urine specimens obtained before labor.Main Outcome MeasureCross-sectional urinary PlGF concentrations, before and after normalization for urinary creatinine.ResultsAmong normotensive controls, urinary PlGF increased during the first 2 trimesters, peaked at 29 to 32 weeks, and decreased thereafter. Among cases, before onset of preeclampsia the pattern of urinary PlGF was similar, but levels were significantly reduced beginning at 25 to 28 weeks. There were particularly large differences between controls and cases of preeclampsia with subsequent early onset of the disease or small-for-gestational-age infants. After onset of clinical disease, mean urinary PlGF in women with preeclampsia was 32 pg/mL, compared with 234 pg/mL in controls with fetuses of similar gestational age (P<.001). The adjusted odds ratio for the risk of preeclampsia to begin before 37 weeks of gestation for specimens obtained at 21 to 32 weeks, which were in the lowest quartile of control PlGF concentrations (<118 pg/mL), compared with all other quartiles, was 22.5 (95% confidence interval, 7.4-67.8).ConclusionDecreased urinary PlGF at mid gestation is strongly associated with subsequent early development of preeclampsia.

Soluble endoglin and other circulating antiangiogenic factors in preeclampsia

Abstract: The circulating antiangiogenic protein soluble fms-like tyrosine kinase 1 (sFltl), also known as soluble vascular endothelial growth factor (VEGF) receptor 1, sequesters the proangiogenic proteins placental growth factor (PlGF) and VEGF. Its circulating level correlates with the severity of preclampsia and with the onset of hypertension or proteinuria. Increased expression of sFltl in pregnant rats creates a state resembling preeclampsia. Soluble endoglin, a coreceptor for transforming growth factors, is another antiangiogenic protein that acts with sFltl to produce a severe preeclampsia-like syndrome in pregnant rats. This nested case-control study, enrolling healthy nulliparous women taking part in the Calcium for Preeclampsia Prevention (CPEP) trial, was designed to show whether endoglin is associated with preeclampsia in humans. Seventy-two women having preeclampsia before 37 weeks' gestation were compared with four groups, each comprising 120 women, who had preeclampsia at term; had gestational hypertension; were normotensive but had an small-for-gestational-age infant; or were normotensive and delivered a normal-sized infant. Severe preeclampsia developed in 61% of women with preterm preeclampsia and 25% of those with preeclampsia at term (after 37 weeks' gestation). Symptomatic women with preterm preeclampsia had significantly higher serum levels of soluble endoglin than control women. Term preeclampsia also was associated with elevated circulating levels of endoglin. At 17-20 weeks' gestation, endoglin levels were significantly higher in women who later developed preterm preeclampsia than in control women. The same was the case at gestational weeks 25 through 28 for women who developed term preeclampsia. Elevated endoglin levels usually were accompanied by an increased sFltl:P1GF ratio. The risk of preeclampsia was greatest for women in the highest quartile of the control distributions for both biomarkers but not for either one alone. On multivariable analysis, large increases in the risk of preeclampsia with a small-for-gestational-age infant were associated with the highest quartile of soluble endoglin or sFltl:P1GF ratio. These findings, combined with those of experimental rodent studies, suggest that circulating soluble endoglin and spil-which cause endothelial dysfunction by different mechanisms-may contribute to the development of preeclampsia. Whether levels of these biomarkers will be useful in predicting the onset of clinical preeclampsia remains to be determined by longitudinal prospective studies.

Vascular endothelial growth factor: basic science and clinical progress.

Abstract: Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen in vitro and an angiogenic inducer in a variety of in vivo models. Hypoxia has been shown to be a major inducer of VEGF gene transcription. The tyrosine kinases Flt-1 (VEGFR-1) and Flk-1/KDR (VEGFR-2) are high-affinity VEGF receptors. The role of VEGF in developmental angiogenesis is emphasized by the finding that loss of a single VEGF allele results in defective vascularization and early embryonic lethality. VEGF is critical also for reproductive and bone angiogenesis. Substantial evidence also implicates VEGF as a mediator of pathological angiogenesis. In situ hybridization studies demonstrate expression of VEGF mRNA in the majority of human tumors. Anti-VEGF monoclonal antibodies and other VEGF inhibitors block the growth of several tumor cell lines in nude mice. Clinical trials with various VEGF inhibitors in a variety of malignancies are ongoing. Very recently, an anti-VEGF monoclonal antibody (bevacizumab; Avastin) has been approved by the Food and Drug Administration as a first-line treatment for metastatic colorectal cancer in combination with chemotherapy. Furthermore, VEGF is implicated in intraocular neovascularization associated with diabetic retinopathy and age-related macular degeneration.

VEGF receptor signalling - in control of vascular function.

Abstract: Vascular endothelial growth-factor receptors (VEGFRs) regulate the cardiovascular system. VEGFR1 is required for the recruitment of haematopoietic precursors and migration of monocytes and macrophages, whereas VEGFR2 and VEGFR3 are essential for the functions of vascular endothelial and lymphendothelial cells, respectively. Recent insights have shed light onto VEGFR signal transduction and the interplay between different VEGFRs and VEGF co-receptors in development, adult physiology and disease.

Soluble endoglin contributes to the pathogenesis of preeclampsia.

Abstract: Preeclampsia is a pregnancy-specific hypertensive syndrome that causes substantial maternal and fetal morbidity and mortality. Maternal endothelial dysfunction mediated by excess placenta-derived soluble VEGF receptor 1 (sVEGFR1 or sFlt1) is emerging as a prominent component in disease pathogenesis. We report a novel placenta-derived soluble TGF-beta coreceptor, endoglin (sEng), which is elevated in the sera of preeclamptic individuals, correlates with disease severity and falls after delivery. sEng inhibits formation of capillary tubes in vitro and induces vascular permeability and hypertension in vivo. Its effects in pregnant rats are amplified by coadministration of sFlt1, leading to severe preeclampsia including the HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome and restriction of fetal growth. sEng impairs binding of TGF-beta1 to its receptors and downstream signaling including effects on activation of eNOS and vasodilation, suggesting that sEng leads to dysregulated TGF-beta signaling in the vasculature. Our results suggest that sEng may act in concert with sFlt1 to induce severe preeclampsia.

Soluble endoglin and other circulating antiangiogenic factors in preeclampsia.

Abstract: Background Alterations in circulating soluble fms-like tyrosine kinase 1 (sFlt1), an antiangiogenic protein, and placental growth factor (PlGF), a proangiogenic protein, appear to be involved in th...

The Inconsistency of “Optimal” Cutpoints Obtained using Two Criteria based on the Receiver Operating Characteristic Curve

Abstract: The use of biomarkers is of ever-increasing importance in clinical diagnosis of disease. In practice, a cutpoint is required for dichotomizing naturally continuous biomarker levels to distinguish persons at risk of disease from those who are not. Two methods commonly used for establishing the "optimal" cutpoint are the point on the receiver operating characteristic curve closest to (0,1) and the Youden index, J. Both have sound intuitive interpretations--the point closest to perfect differentiation and the point farthest from none, respectively--and are generalizable to weighted sensitivity and specificity. Under the same weighting of sensitivity and specificity, these two methods identify the same cutpoint as "optimal" in certain situations but different cutpoints in others. In this paper, the authors examine situations in which the two criteria agree or disagree and show that J is the only "optimal" cutpoint for given weighting with respect to overall misclassification rates. A data-driven example is used to clarify and demonstrate the magnitude of the differences. The authors also demonstrate a slight alteration in the (0,1) criterion that retains its intuitive meaning while resulting in consistent agreement with J. In conclusion, the authors urge that great care be taken when establishing a biomarker cutpoint for clinical use.