Serum Levels Of Placenta Growth Factor Research Articles

Serum and Vitreous Levels of Placenta Growth Factor in Diabetic Retinopathy Patients: Correlation With Disease Severity and Optical Coherence Tomographic Parameters.

Purpose The primary objective of this study was to compare placenta growth factor (PlGF) levels in the serum and vitreous of diabetic retinopathy (DR) patients to non-diabetic controls. Additionally, the study aimed to establish associations between serum and vitreous PlGF concentrations and to examine the correlation between vitreous PlGF in DR patients and morphological parameters. Methods This study included serum and vitreous samples from 38 patients, including 21 patients with DR and 17 non-diabetic controls. The control group included non-diabetic patients with rhegmatogenous retinal detachment with retinal tears secondary to posterior vitreous detachment or trauma. PlGF levels were quantified in vitreous and serum samples using an enzyme-linked immunosorbent assay (ELISA). Optical coherence tomography (OCT) scans from DR patients were evaluated to measure the central retinal thickness (CRT) and macular volume (MV). Results DR patients had significantly higher mean vitreous PlGF levels compared to non-DR patients (70.0±39.2 vs. 46.47±9.7 pg/mL, p-value=0.004). However, no significant increase in mean serum PlGF levels was observed in DR patients (p-value=0.232). Within the DR group, proliferative DR (PDR) patients presented significantly higher vitreous PlGF levels than non-PDR (NPDR) patients (76.5±41.0 vs. 42.5±5.0 pg/mL, p-value=0.009). There was no association between serum and vitreous PlGF levels. The correlation between vitreous PlGF levels and morphological parameters was rsp=0.175, p-value=0.488 for CRT, and rsp=0.288, p-value=0.262 for MV. Conclusion This study emphasizes the important role of PlGF in neovascularization, specifically highlighting its overexpression exclusively in vitreous from PDR patients. The observed increase in PlGF levels may be indicative of disease severity. The lack of correlation between vitreous and serum PlGF levels suggests a potential dissociation between intravitreal and systemic PlGF synthesis. Consequently, targeting PlGF in therapeutic approaches may offer an additional strategy for ocular pathologies with a neovascular component.

Predictive value of vascular endothelial growth factor and placenta growth factor for placenta accreta spectrum

This study aimed to assess the maternal features, Vascular Endothelial Growth Factor (VEGF) and Placenta Growth Factor (PLGF) in the Placenta Accreta Spectrum (PAS); then, to determine a predictive value of VEGF and PLGF in the PAS. This prospective case-control study was conducted on 90 pregnant women including 45 PAS, and 45 Normal Placenta (NP). Maternal age, gravidity, C/S, and serum levels of VEGF and PLGF were assessed between NP and PAS, and among NP and PAS sub-groups, including Placenta Accreta (PA), Placenta Increta (PI), and Placenta Percreta (PP). The Multi-gravidity, previous C/S, maternal age, and serum level of PLGF were significantly higher in the PAS group compared to the NP group OR = 42, 8.1, 1.17, and 1.002 (p-value <.05 for all); however, there was no difference regarding serum level of VEGF (p-value >.05). The same differences were seen among NP with PA, PI, and PP sub-groups (p-value <.05 for all, but p-value >.05 for VEGF). Placenta Previa was uniformly distributed across the PAS sub-groups (p-value >.05), also the VEGF and PLGF serum levels did not differ between PAS with Previa and PAS without Previa groups (p-value >.05). A valid cut-off point for PLGF was reported at 63.55. A predictive value of PLGF for the PAS patients is presented enjoying high accuracy and generalisability for the study population. Impact statement What is already known on this subject? The Placenta Accreta Spectrum (PAS), in which the placenta grows too deep in the uterine wall, is responsible for maternal-foetal morbidity and mortality worldwide; so, the antenatal diagnosis of PAS is an important key to improve maternal-foetal health. Normal placental implantation requires a fine balance among the levels of angiogenic and anti-angiogenic factors, such as the Placenta Growth Factor (PLGF), the Vascular Endothelial Growth Factor (VEGF), and soluble Fms-like tyrosine kinase-1. However, there is still controversy regarding The PLGF and VEGF level changes in PAS patients. What do the results of this study add? Despite traditional measuring the levels of PLGF and VEGF from the placenta at the time of delivery; in this study including 90 participants (28–34 weeks of gestation) the maternal serum levels of PLGF and VEGF were measured in advance (temporality causation), resulted in presenting a more valid cut-off point for PLGF in PAS group. In addition, the serum level of PLGF was significantly higher in the PAS and PAS sub-groups compared to the Normal Placenta group. Also, the Previa status of PAS patients did not affect the VEGF and PLGF serum levels. What are the implications of these findings for clinical practice and/or further research? PLGF cut-off point derived from the maternal serum level could predict PAS validly and, if used as a screening test in an earlier pregnancy, the maternal-foetal morbidity and mortality would decrease.

Using serum placenta growth factor could improve the sensitivity of colorectal cancer screening in fecal occult blood negative population: A multicenter with independent cohort validation study.

BackgroundColorectal cancer (CRC) is one of the most common cancers worldwide. Screening for CRC using the fecal occult blood test (FOBT) is feasible and useful for decreasing disease‐related mortality; however, its sensitivity and compliance are unsatisfactory.MethodsThis study examined the efficacy of using serum placenta growth factor (PlGF) for a novel CRC screening strategy. To investigate a potential novel screening tool for CRC, we compared the sensitivity, specificity, positive predictive value, and negative predictive value of the FOBT, serum PlGF, and their combination through an examination of two independent cohorts and validation using the second cohort. All the patients and control group received the colonoscopy and FOBT, the colonoscopy was used as the gold standard for the result.ResultsSerum PlGF levels were significantly increased in CRC patients (16.8 ± 11.4 pg/mL) compared with controls (12.0 ± 11.2 pg/mL). The predictive model that used the serum PlGF level alone was as effective as the FOBT (AUC: 0.60 vs 0.68, P = 0.891), and it had significantly higher sensitivity than the FOBT (0.81 vs 0.39). In addition, we found serum PlGF level has a good value for predicting CRC patients in those FOBT negative populations. Finally, combining serum PlGF level and the FOBT improved the predictive power and demonstrated satisfactory sensitivity (0.71) and specificity (0.71). This result was confirmed and validated in the second independent cohort. Furthermore, no matter the stages (early/advanced) and the location (distal/proximal) of CRC, the efficacy of serum PlGF and the combined model remained quite stable.ConclusionSerum PlGF level is a potential alternative screening tool for CRC, especially for those who are reluctant to stool‐based screening methods and who were tested as negative FOBT. In addition, combining serum PlGF level and the FOBT could increase the power of CRC screening.

Activation of brown adipocytes by placental growth factor

Gestational diabetes mellitus (GDM) is a type of diabetes and occurs during pregnancy. Brown adipose tissue (BAT) improves glucose homeostasis and mitigates insulin resistance, however, its activity is reduced in GDM. Placenta growth factor (PlGF) is an angiogenic factor produced by placental trophoblasts. Nevertheless, whether and how PlGF could affect BAT function in GDM are not defined. To investigate this question, 91 non-diabetic pregnant participants and 73 GDM patients were recruited to Gynaecology and Obstetrics Centre in Lu He hospital. Serum levels of PlGF were quantified by ELISA. Skin temperature was measured by far infrared thermography in the supraclavicular region where classical BATs were located. The direct effect of PlGF on BAT function was explored using the established human preadipocyte differentiation system. Thereby, we demonstrated that serum levels of PlGF were lower in GDM patients compared with controls, which was accompanied by decreased skin temperature in the supraclavicular region. By qPCR and western blot, mRNA and protein expression of UCP1 and OXPHOS were elevated in differentiated adipocytes treated with PlGF. PlGF stimulated mitochondrion transcription and increased copy number of mitochondrial. When subjected for respirometry, PlGF-treated differentiated adipocytes showed higher oxygen consumption rates than controls. PlGF induced AMPK phosphorylation and blockade of AMPK phosphorylation blunted UCP1 and OXPHOS expression in differentiated adipocytes. PlGF administration reduced cholesterol and triglyceride content in the liver and improved insulin sensitivity in db mice compared with control. In Conclusion, PlGF could activate BAT function. Downregulation of PlGF might contribute to the reduced BAT activity in GDM.

Activation of Browning Adipose Tissues by Placental Growth Factor

Background: Gestational diabetes mellitus (GDM) is a type of metabolic disorders. Browning adipose tissue (BAT) activity is reduced which strengthens insulin resistance in GDM. Placenta growth factor (PlGF) is one of the main factors produced by placenta during pregnancy. Once secreted into circulation, it participates in angiogenesis in peripheral tissues. However, whether and how PlGF modulates BAT function is yet unknown. Methods: We recruited 91 nondiabetic pregnant participants and 73 GDM patients. Serum levels of PlGF were quantified by ELISA. Skin temperature was measured by Far infrared thermography in the supraclavicular region where classical BAT was located. Primary human preadipocytes isolated from intercapsular BAT were differentiated under different concentrations of PlGF in vitro. Terminally differentiated adipocytes were characterized by qPCR, western blot and oxygen consumption rates by respirometry. Phosphorylation signaling pathways in differentiated cells were dissected using Bio-Plex target assay (Bio-Rad). Cells were exposed with 1 ng PlGF in the presence or absence of 1 nM AMPK inhibitor Compound C to assess UCP-1 expression. Results: Serum levels of PlGF were lower in GDM patients than non GDM controls, which was accompanied by decreased skin temperature in the supraclavicular region. By qPCR, PlGF dose-dependently induced BAT marker expression in differentiated brown adipocytes (BAC) and peaked at 1 ng as evidenced by the increased mRNA expression of UCP-1 and Oxphos. The increased BAT marker expression was further confirmed by western blot in differentiated BAC exposed to 1 ng PlGF. Accordingly, PlGF-exposed BAC showed higher oxygen consumption rates than control and stimulated AMPK phosphorylation. Blockade of AMPK phosphorylation abrogated UCP-1 and Oxphos expression in BAC induced by PlGF. Conclusions: Physically, PlGF improves preadipocyte differentiation into active BAC. Decreased PlGF levels might contribute to the reduced BAC activity in GDM. Disclosure R. Yin: None. J. Zhou: None. C. Zhang: None. C. Yan: None. W. Ma: None. N. Wu: None. D. Zhao: None. Y. Feng: None.

The effects of sildenafil citrate on urinary podocin and nephrin mRNA expression in an L-NAME model of pre-eclampsia.

We investigated the effects of sildenafil citrate (SC) on podocyturia in N ω-nitro-L-arginine methyl ester hydrochloride (L-NAME) model of pre-eclampsia (PE). One hundred and twenty Sprague-Dawley rats (SDR) were divided into five groups like pregnant control (PC), early-onset PE (EOPE), late-onset PE(LOPE), early and late-onset PE with SC-treated groups [EOPE (SC); LOPE (SC)]. PE was induced in SDR by oral administration of L-NAME in drinking water for 4-8days for EOPE and 8-14day for LOPE. The blood pressure, urine volume and total urine protein were increased in EOPE and LOPE groups when compared to PC, and all the above parameters decreased in EOPE (SC) and LOPE (SC) groups when compared to EOPE and LOPE groups, respectively. The EOPE and LOPE groups showed an increase in urinary nephrin mRNA and podocin mRNA levels compared to PC group. Increases in serum and renal soluble fms-like tyrosine kinase-1 (sFlt-1) expression levels and decreases in renal vascular endothelial growth factor (VEGF) expression and serum placenta growth factor (PlGF) levels were observed in EOPE and LOPE groups when compared to PC group. In addition, decreases in serum and renal sFlt-1 expression levels and increases in renal VEGF expression and serum PlGF levels were observed in EOPE (SC) and LOPE (SC) groups when compared to EOPE and LOPE groups, respectively. The light microscopy showed that the renal tissue of L-NAME-treated rats had extensive glomerular damage, tubular damage and infiltration by mononuclear cells when compared to PC group. Therefore, SC ameliorated podocyturia through its effects on the antiangiogenic/angiogenic status in this animal model.

Lack of evidence for PlGF mediating the tumor resistance after anti-angiogenic therapy in malignant gliomas.

Placenta growth factor (PlGF) is a member of vascular endothelial growth factor family which can promote cancer growth by various mechanisms. Placenta growth factor is upregulated in many neoplastic diseases and serum levels of PlGF are increased in cancer patients following anti-angiogenic therapy. However, its role in glioma growth is yet not fully elucidated. In this study we analyzed the expression of PlGF mRNA using real time PCR in human gliomas of different WHO grades. Placenta growth factor mRNA levels were highly variable and did not correlate with WHO grades, arguing against a significant role in glioma progression. The highest PlGF expression was observed in anaplastic astrocytomas whereas grade II astrocytomas and glioblastomas displayed lower levels of expression. Immunohistochemical analysis showed that PlGF was expressed by inflammatory and endothelial cells in addition to tumor cells. Placenta growth factor mRNA expression in 12 matched glioblastoma samples before and after therapy, including bevacizumab and cilengitide treatment was largely unaffected by the aforementioned treatment modalities. In vitro, the exposure of VEGFR-1 expressing glioma cells to bevacizumab did not increase the expression levels of PlGF mRNA. In summary, our results do not support the hypothesis that PlGF plays a major role in the resistance of gliomas after anti-angiogenic therapy.

Clinical significance of assessment of thrombospondin and placenta growth factor levels in patients with sickle cell anemia: two centers egyptian studies.

BackgroundSickle cell disease has a worldwide distribution. Vaso-occlusive crisis (VOC) is one of the most important clinical features of the disease. Thrombospondin (TSP1) and Placenta growth factor (PlGF) have been reported to be involved in sickle cell diseases (SCD).ObjectiveThe aim of this study was to assess the clinical significance of Thrombospondin and Placenta growth factor profiles in patients with sickle cell disease.Patients and methodsThis study was carried out in sixty patients with sickle cell anemia who were attendants to Hematology units, Pediatric Departments, Tanta and Elmenofia University Hospitals in the period between December 2011 and May 2014 including thirty patients during vaso-occlusive crisis and thirty patients out of crisis. Also this study included twenty healthy children of matched age and sex as a control group. Serum TSP1 and PlGF levels were analyzed by ELISA.ResultsIn SCA patients with crisis the mean serum Thrombospondin level was 902.5±280.89 ng/mL; in SCA patients out of crisis the mean serum Thrombospondin level was 462.5 ± 190.2 ng/mL and in controls the mean value was 236.66±58.29 ng/mL. In SCA patients with crisis the mean serum Placenta growth factor level was 19.97±1.28 pg/ml; in SCA patients out of crisis the mean serum Placenta growth factor level was 13.12 ± 1.82 pg/ml and in controls the mean value was 9.89 ± 1.20 pg/ml. All paired comparisons for Thrombospondin and Placenta growth factor reached statistical significance (P< 0.001). There was significant positive correlation between serum Thrombospondin and Placenta growth factor levels in sickle cell anemia patients during crisis (r=0.848, p=<0.001).ConclusionsThis is the first study to show TSP1and PlGF concentration changes in patients with SCD in a large cohort study from Middle East, and to show correlation between both markers; therefore TSP1and PlGF may be useful VOC markers in SCD patients.RecommendationTo further assess TSP1 and PlGF as a marker of VOC in patients with SCD, further studies should be conducted to determine the exact point before VOC, when serum TSP1 and PIGF levels begin to increase. This requires monitoring of the TSP1 and PIGF levels in sickle cell patients out of crisis, showing how rapidly these levels increase just before VOC development.

OP0268 Prediction of Cardiac and Vascular Events in Systemic Sclerosis: Input from Endothelin-1 Type A Receptor Antibodies

BackgroundCardiac and peripheral microvascular alterations are key features of systemic sclerosis (SSc). We have previously reported that angiogenic markers can predict the cardiovascular outcomes in SSc [1]. In parallel, a...

Serum Levels of Three Angiogenic Factors in Systemic Lupus Erythematosus and Their Clinical Significance

Our research investigates the serum levels of three angiogenic factors in the AF family, namely, placenta growth factor (PlGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF), in 54 patients with SLE (SLE group) and 28 healthy controls (normal control) through ELISA measurement. And their interrelationships were also systematically analyzed. The SLE patients were then divided into active SLE group and inactive SLE group according to the SLEDAI score. The results show that serum levels of PlGF, bFGF, and VEGF in all SLE group and active SLE group were higher than those in normal controls. Serum levels of PlGF and bFGF in inactive SLE group were higher than those in normal controls. The level of PlGF was positively correlated with VEGF in SLE patients and positive correlation is also shown in bFGF with VEGF. The levels of PlGF and VEGF in SLE patients were positively correlated with both ESR and SLEDAI score. Thus a tentative conclusion can be drawn that the serum levels of the angiogenic factors, for example, PlGF, bFGF, and VEGF, may be relevant in the pathogenesis of SLE, and the concentrations of PlGF and VEGF seem to be the markers of SLE activity.

SAT0216 Low Reactive Hyperemia Index Assessed By Endo-Pat And High Serum Placenta Growth Factor Associate With Vasculopathy And Disease Progression In Patients With Systemic Sclerosis

BackgroundVasculopathy and progressive disease status such as digital ulcer, pulmonary arterial hypertension and pulmonary fibrosis deteriorate the quality of life as well as survival rate in patients with systemic sclerosis...

Examining the correlation between placental and serum placenta growth factor in preeclampsia

Decreased levels of serum placenta growth factor (PlGF) are associated with preeclampsia. We sought to determine whether serum and placental levels of PlGF (sPlGF and pPlGF) are associated with preeclampsia and whether there is a correlation between serum and placental PlGF levels. These analyses were part of a larger, prospective, case-control study. Cases were women with preeclampsia. Controls were women without preeclampsia who delivered at term. Analyses included nonparametric tests to compare medians, logistic regression to estimate odds, and calculation of correlation coefficients. Twenty-four cases (10 preterm, 14 term) were compared with 14 controls. Median levels of PlGF were significantly lower in cases than controls (pPlGF: 232.6 vs 363.4 pg/mL, P = .02; sPlGF: 85.5 vs 274.4 pg/mL, P < .001). Serum and placental PlGF were correlated (overall: 39%, P = .006; cases with preterm preeclampsia and growth restriction: 87%, P = .02). Serum and placental PlGF are independently associated with preeclampsia and correlated with each other.

Preoperative serum placenta growth factor level as a new marker for stage II or III colorectal cancer patients

We first reported in this study that serum placenta growth factor and carcinoembryonic antigen in combination were useful markers for selecting early-stage colorectal cancer patients. The aim of the present study was to determine whether serum placenta growth factor could provide carcinoembryonic antigen-independent prognostic information on patients undergoing curative surgery. Serum and tissue samples were collected from 158 patients with colorectal cancer and from 50 controls. Serum and tissue levels of placenta growth factor were measured by enzyme-linked immunosorbent assay. The serum placenta growth factor levels in colorectal cancer patients were compared with those in healthy controls, and we retrospectively assessed the association between serum placenta growth factor levels and clinicopathological findings and survival. Expression of placenta growth factor was significantly higher in colorectal cancer tissues compared with non-tumor tissues. The mean serum placenta growth factor level in patients was significantly higher than that in controls and significantly higher in patients with large tumor, lymph-node involvement and distant metastasis. Elevated serum placenta growth factor levels are significantly associated with colorectal cancer development, lymph or distant invasive phenotypes and survival, especially in stage II or III patients.

Increased serum placenta growth factor level is significantly associated with progression, recurrence and poor prognosis of oral squamous cell carcinoma

We recently found that the expression of placenta growth factor (PlGF) in oral squamous cell carcinoma (OSCC) specimens is correlated with the progression and prognosis of OSCC. In this study, serum samples were obtained from 72 OSCC patients before and 3 months after surgical cancer excision and from 30 normal controls. Serum PlGF levels were determined by enzyme-linked immunosorbent assay (ELISA). The mean serum PlGF levels were significantly higher in pre-surgery OSCC patients than in normal controls (19.1±10.7 vs. 10.1±4.5, P<0.001). Serum PlGF levels dropped to near the normal control levels after surgical cancer removal. Higher pre-surgery serum PlGF levels were significantly associated with larger tumor size (P=0.015), positive lymph node metastasis (P=0.001), more advanced clinical stages (P=0.002), and loco-regional recurrence (P=0.037). The serum PlGF level was identified as an independent unfavorable prognosis factor by multivariate Cox regression analyses (P=0.014). Kaplan-Meier curve showed that OSCC patients with a higher serum PlGF level had a significantly poorer cumulative recurrence-free survival than those with a lower serum PlGF level (log-rank test, P=0.009). When we used the serum PlGF level of 19.1 pg/ml (mean normal control value plus 2 standard deviations) as a cutoff point, the sensitivity, specificity, and positive predictive value for tumor recurrence was 80%, 56% and 78%, respectively. We conclude that the serum PlGF level may be a valuable biomarker for prediction of therapeutic effect, progression, recurrence and prognosis of OSCC.

The ratio of serum placenta growth factor to soluble vascular endothelial growth factor receptor-1 predicts the prognosis of hepatocellular carcinoma

Angiogenesis plays crucial roles in development and progression of hepatocellular carcinoma (HCC). Placenta growth factor (PLGF), belonging to vascular endothelial growth factor (VEGF) family, is involved in angiogenesis associated with cancer. Soluble VEGF receptor-1 (sVEGFR1) has been thought to be an intrinsic negative regulator for PLGF. We investigated whether serum PLGF and serum sVEGFR1 is associated with prognosis of HCC. Serum PLGF and sVEGFR1 levels were measured in 145 patients with HCC using enzyme-linked immunosorbent assay. The levels of these factors and the ratio of PLGF to sVEGFR1 were analyzed in relation with clinical parameters. The higher level of sVEGFR1 and the lower ratio of PLGF/sVEGFR1 were significantly associated with poor survival in HCC. Cox regression analysis revealed that the lower ratio of PLGF/sVEGFR1 independently correlated to prognosis of patients with HCC. The ratio of PLGF/sVEGFR1 was independent prognostic indicator for HCC. The ratio of PLGF/sVEGFR1 should be addressed in anti-angiogenic therapy for HCC.

Elevated serum placenta growth factor (PlGF) levels in patients with systemic sclerosis: A possible role in the development of skin but not lung fibrosis

Elevated serum placenta growth factor (PlGF) levels in patients with systemic sclerosis: A possible role in the development of skin but not lung fibrosis

Preoperative Serum Placenta Growth Factor Level Is a Prognostic Biomarker in Colorectal Cancer

Increased angiogenesis at the site of the primary tumor in colorectal cancer has been associated with poor prognosis and relapse of disease. We previously demonstrated that the tissue level of placenta growth factor expression was upregulated in colorectal cancer and correlated with disease progression and patient survival. The aims of this study are to examine the prognostic value of serum placenta growth factor, vascular endothelial growth factor, and sFlt-1 and to compare them with the carcinoembryonic antigen levels in patients with colorectal cancer. Preoperative serum from 86 patients and serum from 30 healthy controls was included. The levels of sFlt-1, placenta growth factor, vascular endothelial growth factor in the serum were assayed and correlated with the clinical stage results. Serum placenta growth factor, but not vascular endothelial growth factor, increased; sFlt-1 decreased in patients with preoperative colorectal cancer, compared with healthy controls. Higher preoperation serum placenta growth factor levels were associated with higher risk of recurrence. Preoperation serum placenta growth factor, but not carcinoembryonic antigen, was a prognostic indicator in patients with Stage III colorectal cancer. When we use the median level (20.6 pg/ml) of preoperative serum placenta growth factor as a cutoff point, the sensitivity, specificity, and positive predictive value for tumor recurrence and survival was 80, 54, 80% and 70, 56, 70%, respectively. Preoperative serum placenta growth factor levels were higher in patients with colorectal cancer, were negatively correlated with the serum sFlt-1, and could be used as a prognostic indicator for recurrence and survival for colorectal cancer.

Increased expression of placenta growth factor in COPD

Background:Vascular endothelial growth factor (VEGF) and its receptor may have an important role in the pathogenesis of emphysema. The effect of another angiogenic factor, placenta growth factor (PlGF), in chronic...

Correlations of placental perfusion and PlGF protein expression in early human pregnancy

The purpose of this study was to investigate temporal correlations between maternal serum placenta growth factor levels and placental perfusion in early human pregnancies. Systolic umbilical artery Doppler blood flow velocity indices at fetal and placental insertion sites were measured between 7 and 22 weeks of gestation from normal singleton pregnancies. Maternal serum placenta growth factor levels were determined by enzyme-linked immunosorbent assay. Maternal serum placenta growth factor levels showed an exponential increase at approximately 14 weeks of gestation. Placenta perfusion, as estimated by systolic Doppler blood flow indices, significantly increased with gestational age (P < .0001). There was a close association between placenta growth factor expression levels and evidence of increased placenta perfusion (P < .033). The significant increase in serum placenta growth factor coincides with the increased perfusion of the maternal/fetal interface at approximately 12 to 14 weeks of gestation. Correlation of placenta growth factor expression and placental perfusion suggests that placenta growth factor may contribute to assuring adequate vascular development/function of the placenta early in gestation.

Vascular Growth Factors in Patients with Sickle Cell Disease.

Angiogenesis plays a central role in neovascular processes. In sickle cell patients neovascularization is considered a common feature that is associated with complications such as retinopathy and cerebrovascular disease. Several studies have reported increased vascular growth factor levels such as vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF) in small groups of patients. Recently the angiopoietin/Tie2 system has been shown to be of major importance in vessel maturation. In order to thoroughly characterize vascular growth factor profiles in sickle cell patients we analyzed serum levels of VEGF, PlGF, Angiopoietin-1, Angiopoietin-2, Tie-2 and erythropoietin (EPO) during the asymptomatic phase as well as during painful crises in HbSS patients (n=42) and compared these to levels in HbAA controls (n=30). Also, levels were compared between patients with and without a history of acute vaso-occlusive complications the year prior to sample collection. Serum Angiopoietin-2, Tie-2 and EPO levels were significantly higher in sickle cell patients as compared to controls (p<0.01, p=0.03 and p<0.01 respectively), whereas PlGF and VEGF serum levels were similar between patients and controls (p= 0.21 and p=0.5). Only Angiopoietin-2 and EPO serum levels were significantly increased in sickle cell patients during acute vaso-occlusive crises as compared to levels in asymptomatic patients (p<0.01 and p=0.03 respectively). No differences were detected in measured parameters between patients with a history of acute vaso-occlusive complications as compared to patients without acute vaso-occlusive complications in the preceding year. Our results show a specific pattern of angiopoietins in sickle cell patients. Considering the importance of endothelial cell activation in sickle cell disease and the regulation of endothelial cell survival and blood vessel maturation by the angiopoietin/Tie-2 system, further analysis of angiogenesis in sickle cell disease is warranted.