Risk ractors for the occurrence of preeclampsia and the predictive value of serum VEGFR-1 and PLGF for preeclampsia / 中国医师杂志

Objective:To explore the risk factors for the occurrence of preeclampsia (PE) and the predictive value of serum vascular endothelial growth factor receptor-1 (VEGFR-1) and placental growth factor (PLGF) for PE.Methods:A retrospective study was conducted to select 148 pregnant women who underwent prenatal examinations at the First People′s Hospital of Chenzhou from January 2020 to January 2022 and were ultimately diagnosed with PE as the PE group, and 148 healthy pregnant women who underwent prenatal examinations during the same period as the PE group were selected as the control group. The levels of VEGFR-1, PLGF, and VEGFR-1/PLGF were compared between two groups of pregnant women. Logistic regression analysis was performed on the risk factors for PE, and the correlation between VEGFR-1, PLGF, VEGFR-1/PLGF and risk factors was analyzed. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of VEGFR-1, PLGF, and VEGFR-1/PLGF for PE and obtain cutoff values. The survival curve of pregnant women with PE was plotted based on the cutoff values.Results:The levels of VEGFR-1 and VEGFR-1/PLGF in the PE group were higher than those in the control group (all P<0.05), while the levels of PLGF were lower than those in the control group ( P<0.05). Logistic regression analysis showed that age, body mass index (BMI), pregnancy induced hypertension, pregnancy induced diabetes, family history of hypertension, preeclampsia, VEGFR-1 and VEGFR-1/PLGF were risk factors for PE (all P<0.05), and PLGF was a protective factor for PE ( P<0.05). VEGFR-1, VEGFR-1/PLGF were positively correlated with age, BMI, pregnancy induced hypertension, pregnancy induced diabetes, hypertension family history, and PE (all P<0.001), while PLGF was negatively correlated with age, BMI, pregnancy induced hypertension, pregnancy induced diabetes, hypertension family history, and preeclampsia (all P<0.001). VEGFR-1, PLGF, and VEGFR-1/PLGF had higher predictive value for PE (AUC=0.773, 0.791, 0.825), with cutoff values of 9190.83 ng/L, 508.17 ng/L, and 21.64, respectively. According to the cutoff value, 296 pregnant women were divided into three groups: low, medium, and high risk. The survival analysis results showed that the probabilities of PE occurrence in the three groups were 1.36%, 18.97%, and 66.67%, respectively. Conclusions:VEGFR-1 and PLGF have high predictive value for PE, and clinical monitoring of VEGFR-1/PLGF levels combined with other examination methods can improve the accuracy of PE diagnosis and prediction, and improve pregnancy outcomes.

La aplicación de factores de crecimiento en el desarrollo de la Ingeniería de tejidos óseos / Application of growth factors in the development of bone tissue engineering

RESUMEN Introducción: los avances científico-técnicos en el campo de la Biología celular y molecular han permitido restaurar y mejorar la función de órganos y tejidos lesionados por ciertas enfermedades y traumatismos. La Ingeniería de tejido se define como el uso de los principios y métodos de la Ingeniería, la Biología y la Bioquímica, los cuales están orientados a la comprensión de la estructura y la función de los tejidos normales y patológicos, y al consecuente desarrollo de sustitutos biológicos para restaurar, mantener o mejorar su función. Objetivo: realizar un acercamiento a algunos aspectos de la Biología celular y molecular vinculada con la Ingeniería tisular ósea. Métodos: se realizó una búsqueda bibliográfica en SciELO Cuba y en Google académico durante el período de 1 de marzo al 28 de abril de 2018. Se evaluaron 134 artículos y el estudio se circunscribió a los 25 artículos que se enfocaban en estas temáticas de manera integral. Conclusiones: se ofreció una visión general de los avances que se han obtenido en la Biología celular y molecular, y en particular a: la aplicación de los factores de crecimiento en la Ingeniería del tejido óseo, así como sus futuras perspectivas. Se concluyó que es fundamental consolidar una base apropiada de conocimientos sobre la Biología celular y molecular y el desarrollo actual de la Ingeniería del tejido óseo.

ABSTRACT Introduction: scientific and technical advances in the field of cellular and molecular biology have allowed restoring and improving the function of organs and tissues injured by certain diseases and trauma. Tissue engineering is defined as the use of the principles and methods of Engineering, Biology and Biochemistry, which are aimed at understanding the structure and function of normal and pathological tissues, and the consequent development of biological substitutes to restore, maintain or improve their function. Objective: to carry out an approach to some aspects of cellular and molecular biology related to bone tissue engineering. Methods: a bibliographic review was carried out in SciELO Cuba and Google Scholar from March 1 to April 28, 2018. A number of 134 articles were evaluated and the study was limited to 25 articles that focused on these topics in an integral way. Conclusions: an overview of the advances that have been obtained in cellular and molecular biology was offered, particularly to the application of growth factors in bone tissue engineering, as well as its future perspectives. We concluded that it is essential to consolidate an appropriate knowledge base on cellular and molecular biology and the current development of bone tissue engineering.

Corrección de los múltiplos de la mediana de los biomarcadores del modelo de predicción de preeclampsia de la Fetal Medicine Foundation para población mexicana / Correction of the multiples of median of the biomarkers used in the Fetal Medicine Foundation's prediction model for preeclampsia in Mexican population

Resumen OBJETIVO: Calcular y ajustar los múltiplos de la mediana para el índice de pulsatilidad medio de las arterias uterinas, presión arterial media materna, factor de crecimiento placentario y proteína plasmática A asociada al embarazo, a fin de valorar el desempeño diagnóstico del modelo corregido de preeclampsia de la Fetal Medicine Foundation en población mexicana. MATERIALES Y MÉTODOS: Estudio de casos y controles anidado en una cohorte prospectiva efectuado en el Centro de Salud Dr. Galo Soberón y Parra entre el 1 de octubre de 2015 y el 30 de junio de 2016. Criterio de inclusión: pacientes con embarazo de 11-13.6 semanas. Criterio de exclusión: pacientes de riesgo no seleccionado, con embarazo único, entre 11 y 13.6 semanas calculadas por ecografía mediante longitud cráneo cauda. Criterio de eliminación: pacientes que abandonaron el estudio. Se evaluaron el índice de pulsatilidad medio de las arterias uterinas, la presión arterial media, los valores séricos del factor de crecimiento placentario y la proteína plasmática A asociada al embarazo. Se comparó la diferencia en la distribución de los biomarcadores entre la observada en población mexicana y la esperada según la formula original de la Fetal Medicine Foundation. Cuando la diferencia fue mayor a 0.2 múltiplos de la mediana, se utilizó la mediana del observado como coeficiente de ajuste a la fórmula original del esperado. RESULTADOS: De las 300 pacientes reclutadas, 292 concluyeron el estudio. La media de semanas de embarazo al momento del tamizaje fue de 12.4 (desviación estándar 0.72). La prevalencia de preeclampsia fue de 4.5% (13 de 292). Se encontraron diferencias importantes en la distribución de múltiplos de la mediana para el índice de pulsatilidad medio de las arterias uterinas, factor de crecimiento placentario y proteína plasmática A asociada al embarazo. Posterior a la corrección de los biomarcadores, la sensibilidad, falsos positivos y área bajo la curva del modelo ajustado para detectar cualquier preeclampsia fue de 92% (12 de 13), 5.7% (16 de 279) y 93.3%, respectivamente. CONCLUSIONES: La distribución de los múltiplos de la mediana en población mexicana es distinta para los biomarcadores: factor de crecimiento placentario, proteína plasmática A asociada al embarazo e índice de pulsatilidad medio de las arterias uterinas. El ajuste de estos biomarcadores para población mexicana resulta en un buen desempeño diagnóstico del modelo de preeclampsia.

Abstract OBJECTIVE: Calculate and adjust the multiples of the median (MoMs) for the mean pulsatility index of uterine arteries (IPm Aut), mean arterial pressure (PAM), placental growth factor (PlGF) and plasma protein associated with pregnancy (PAPP-A), in order to assess the diagnostic performance of the corrected preeclampsia model of the fetal medicine foundation in the Mexican population. MATERIALS AND METHODS: Case-control study nested in a prospective cohort conducted at the "Dr. Galo Soberón y Parra "from October 1, 2015 - June 30, 2016. Patients with pregnancy of 11-13.6 weeks were included, multiple pregnancies or older than 14 weeks were excluded and patients with medication intake prior to pregnancy; Patients who decided to leave the study were eliminated. Autm IPm, PAM, PlGF and PAPP-A serum values were evaluated. The difference in the distribution of biomarkers between that observed in the Mexican population and that expected was compared according to the original formula of the Fetal Medicine Foundation. When the difference was greater than 0.2 MoMs, the median observed was used as an adjustment coefficient to the original expected formula. RESULTS: Of the 300 patients recruited, 292 concluded the study. The average gestational age at the time of screening was 12.4 weeks (standard deviation [SD] 0.72). The prevalence of preeclampsia was 4.5% (13/292). Important differences were found in the distribution of multiples of the median (MoMs) for IPm Aut, PlGF and PAPP-A. After correction of the biomarkers, the sensitivity, false positives and area under the curve (AUC) of the model adjusted to detect any preeclampsia was 92% (12/13), 5.7% (16/279) and 93.3%, respectively . CONCLUSIONS: The distribution of MoMs in the Mexican population is different for the PlGF, PAPP-A and IPm Aut biomarkers. The adjustment of these biomarkers to the Mexican population results in a good diagnostic performance of the preeclampsia model.

Different effects of pravastatin on sFlt-1, PlGF and VEGF in different preeclampsia-like mouse models / 中华妇产科杂志

Objective@#To explore the pathways of preeclampsia by investigating different effects of pravastatin (Pra) on and soluble FMS tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) in different preeclampsia (PE)-like mouse models.@*Methods@#C57BL/6J mice were randomly subcutaneously injected with N-nitro-L-arginine methyl ester (L-NAME) or intraperitoneally injected with lipopolysaccharide (LPS) as PE-like mouse model, saline as normal pregnancy control (Con) respectively, daily at gestational 7-18 days. Pra was given daily at gestational 8-18 days in each model group and the mice were divided into Pra (L-NAME+Pra, LPS+Pra, Con+Pra) and saline (L-NAME+NS, LPS+NS, Con+NS) groups. Liver,placental tissue and blood of pregnant mice were collected on the 18th day of pregnancy. The levels of VEGF, PlGF and sFlt-1 in the liver, placenta and serum of mice in each group were compared by western blot, ELISA and real-time fluorescence quantitative PCR (RT-PCR).@*Results@#(1) ELISA: Serum VEGF (205.70±3.43, 154.60±2.31) and PlGF (131.5±3.75, 101.50±4.31) levels were significantly increased in L-NAME+Pra group compared with L-NAME+NS group (all P<0.05). Serum VEGF (202.30±4.90, 144.50±6.71) and PlGF (121.50±3.86, 95.41±4.08) levels were significantly higher in LPS+Pra group than those in LPS+NS group (all P<0.05). Serum sFlt-1 level in LPS+Pra group was significantly lower than that in LPS+NS group (3.01±0.50, 776.60±80.06), serum sFlt-1 level in L-NAME+Pra group was significantly lower than that in L-NAME+NS group (2.60±0.06, 583.70±9.83; all P<0.05). (2) Western blot: the expression levels of PlGF (1.344±0.118, 0.664±0.143) and VEGF (1.34±0.12, 0.66±0.14) in the liver of mice in the L-NAME+Pra group were significantly higher than those in the L-NAME+NS group (all P<0.05), but the expression levels of PlGF and VEGF in the placenta of L-NAME+Pra group were not significantly different from those of L-NAME+NS group (all P>0.05). The expression levels of PlGF and VEGF in placenta and liver of pregnant mice in LPS+Pra group were not significantly different from those in LPS+N group (all P>0.05). (3) RT-PCR: the mRNA expression of PlGF and VEGF in placenta and liver of L-NAME+Pra group were not significantly different from those in L-NAME+NS group (all P>0.05). The mRNA expression levels of PlGF and VEGF in placenta and liver of LPS+Pra group were not significantly different from those of LPS+NS group (all P>0.05).@*Conclusions@#Pra has different regulatory effects on vascular endothelial function in different PE-like models. It reveals that different pathogenesis and pathways exist in different PE-like changes.

Progress in the study for pathogenesis and clinical treatment of preeclampsia / 解放军医学杂志

Preeclampsia (PE) is a serious complications during pregnancy, with a global incidence of 2%–8%. It is one of the important causes of the incidence and death of pregnant women and parturients. The main clinical manifestations are hypertension (systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg), proteinuria (>0.3 g/24 h) can be accompanied by renal dysfunction, thrombocytopenia, liver dysfunction, pulmonary edema and other multi-system and multiple organ involvement. Antiphospholipid antibody syndrome, hypertension, diabetes, chronic kidney disease, obesity, PE family history, multiple pregnancy, maternal old age are the risk factors of PE. At present, the pathogenesis of PE is not completely clear, but more and more evidences suggest that the abnormal level of angiogenic factors and coagulation dysfunction are the main causes of the disease. The research progress in recent years has been reviewed in present paper in the pathogenesis and clinical treatment of PE, so as to provide a reference for clinical use.

Different effects of pravastatin on sFlt?1, PlGF and VEGF in different preeclampsia?like mouse models / 中华妇产科杂志

Objective To explore the pathways of preeclampsia by investigating different effects of pravastatin (Pra) on and soluble FMS tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) in different preeclampsia (PE)?like mouse models. Methods C57BL/6J mice were randomly subcutaneously injected with N?nitro?L?arginine methyl ester (L?NAME) or intraperitoneally injected with lipopolysaccharide (LPS) as PE?like mouse model, saline as normal pregnancy control (Con) respectively, daily at gestational 7-18 days. Pra was given daily at gestational 8-18 days in each model group and the mice were divided into Pra (L?NAME+Pra, LPS+Pra, Con+Pra) and saline (L?NAME+NS, LPS+NS, Con+NS) groups. Liver,placental tissue and blood of pregnant mice were collected on the 18th day of pregnancy. The levels of VEGF, PlGF and sFlt?1 in the liver, placenta and serum of mice in each group were compared by western blot, ELISA and real?time fluorescence quantitative PCR (RT-PCR). Results (1) ELISA: Serum VEGF (205.70±3.43, 154.60±2.31) and PlGF (131.5±3.75, 101.50± 4.31) levels were significantly increased in L?NAME+Pra group compared with L?NAME+NS group (all P<0.05). Serum VEGF (202.30 ± 4.90, 144.50 ± 6.71) and PlGF (121.50 ± 3.86, 95.41 ± 4.08) levels were significantly higher in LPS+Pra group than those in LPS+NS group (all P<0.05). Serum sFlt?1 level in LPS+Pra group was significantly lower than that in LPS+NS group (3.01±0.50, 776.60±80.06), serum sFlt?1 level in L?NAME+Pra group was significantly lower than that in L?NAME+NS group (2.60±0.06, 583.70±9.83;all P<0.05). (2) Western blot: the expression levels of PlGF (1.344±0.118, 0.664±0.143) and VEGF (1.34±0.12, 0.66 ± 0.14) in the liver of mice in the L?NAME+Pra group were significantly higher than those in the L?NAME+NS group (all P<0.05), but the expression levels of PlGF and VEGF in the placenta of L?NAME+Pra group were not significantly different from those of L?NAME+NS group (all P>0.05). The expression levels of PlGF and VEGF in placenta and liver of pregnant mice in LPS+Pra group were not significantly different from those in LPS+N group (all P>0.05). (3) RT?PCR: the mRNA expression of PlGF and VEGF in placenta and liver of L?NAME+Pra group were not significantly different from those in L?NAME+NS group (all P>0.05). The mRNA expression levels of PlGF and VEGF in placenta and liver of LPS+Pra group were not significantly different from those of LPS+NS group (all P>0.05). Conclusions Pra has different regulatory effects on vascular endothelial function in different PE?like models. It reveals that different pathogenesis and pathways exist in different PE?like changes.

Clinical efficacy of sorafenib in treatment of primary hepatic carcinoma and its effects on serum VEGFR -2 and PLGFlevels / 临床肝胆病杂志

To investigate the clinical efficacy of sorafenib in the treatment of primary hepatic carcinoma (PHC) and its effects on serum vascular endothelial growth factor receptor -2 (VEGFR -2) and placental growth factor (PLGF) levels.Methods A total of 110 patients with a confirmed diagnosis of PHC who received treatment in Jinshan Hospital Affiliated to Fudan University from July 2014 to March 2016 were randomly and equally divided into observation group and control group .The control group was given routine treatment, while the observation group received sorafenib in addition to the routine treatment .Serum levels of VEGFR -2 and PLGF were measured by ELISA.Liver function parameters, aspartate aminotransferase (AST), prothrombin time (PT), total bilirubin (TBil), albumin (Alb), and alanine aminotransferase (ALT), were also recorded.Comparison of continuous data between groups was made by independent samples t -test, and the changes in continuous data after intervention in each group were evaluated by paired samples t -test.Comparison of categorical data between groups was made by chi -square test.Results The observation group showed significant reductions in serum VEGFR -2 and PLGF levels after treatment (VEGFR -2: 7053.2 ±1836.1 ng/L vs 8721.4 ±2427.8 ng/L, t =4.089, P <0.001; PLGF: 468.4 ±136.5 pg/ ml vs 656.8 ±191.4 pg/ml, t =5.975, P <0.001).After treatment, the observation group had significantly lower serum VEGFR -2 and PLGF levels than the control group (VEGFR -2: 7053.2 ±1836.1 ng/L vs 8097.5 ±2325.4 ng/L, t =2.64, P <0.05; PLGF: 468.4 ± 136.5 pg/ml vs 643.3 ±195.8 pg/ml, t =2.48, P <0.05).The observation group showed significant changes in serum AST and ALT lev - els after treatment (t =4.302 and 3.097, both P <0.05).After treatment, the observation group had significantly lower serum AST and ALT levels than the control group (t =2.56 and 2.39, both P <0.05).Compared with the control group, the observation group had better follow -up results, with a significantly increased disease control rate (27.3% vs 47.3% , χ2 =4.705, P =0.030), and had a significantly higher survival rate at 40 months after treatment (43.6% vs 69.1%, χ2 =7.245, P =0.007).Conclusion Sorafenib is effective in the treatment of PHC patients, as it can significantly reduce the serum levels of VEGFR -2 and PLGF, prolong the survival time of patients, and improve the prognosis of patients.

Placental growth factor: a useful predictable marker in predicting preeclampsia / 中华检验医学杂志

The placental growth factor ( PlGF) is a kind of glycoprotein with four isoforms , which is predominantly expressed in the placenta . The PlGF plays an important role in the angiogenesis and development , as a biomarker of placenta angiogenesis , the decreasing of the PlGF expression may lead to the dysfunction of vascularization .Anti-angiogenesis is a pathological characteristic of pre-eclampsia.The PlGF levels both in the serum and urine are lower in preeclampsia than those in normal pregnancy .Due to the decreasing of PlGF during the first trimester , the PlGF is an important predictable marker of preeclampsia .It is also expected to be used in the treatment of preeclampsia .

The effect of captopril and losartan on paraquat-induced pulmonary fibrosis and PlGF expression in the lungs of rats / 中华劳动卫生职业病杂志

Objective@#To investigate the dynamic expression of placenta growth factor (PlGF) in the lungs and its role in paraquat-induced pulmonary fibrosis and to evaluate the effect of ACEI captopril and AT (1) -receptor blocker losartan on paraquat-induced pulmonary fibrosis.@*Methods@#84 adult healthy female Sprague-Dawley (SD) rats were randomly divided into four groups of different treatments designated as: Control, PQ alone (PQ) , captopril treatment, losartan treatment. Each group was divided into three subgroups of seven animals each. The animals were killed at either 7, 14 or 28 days after PQ administration. The rats in PQ group, treatment group were treated intragastrically (ig) with PQ (40 mg/kg) and the rats in control group were treated with the same dose of saline at the beginning of the experiment. The treatment group received Captopril (60 mg/kg; ig) or Losartan (10 mg/kg; ig) once a day respectively after PQ administration and the other two groups received saline. At the given timepoint, animals were sacrificed and lungs were harvested. A semiquantitative assay of histological examination, hydroxyproline in lung tissues were used to determine the severity of alveolitis and fibrosis. RT-PCR and immunohistochemistry were used to detect the mRNA and protein expression of PlGF.@*Results@#Inflammatory cell infiltration and fibrotic scores were more prominent in the model group, hydroxyproline contents in lung tissue were significantly increased after PQ administration compared to the control group. Captopril, losartan apparently attenuated the degree of lung injury and pulmonary fibrosis. On 7th, 14th days, the levels of alveolitis in the intervention groups were significantly alleviated as compared with the model group (P<0.05) . On 28th days, the levels of pulmonary fibrosis in the intervention groups were significantly alleviated as compared with model group (P<0.05) . The hydroxyproline contents in the intervention groups were significantly decreased as compared with model group (P<0.01) . PlGF mRNA on day 7, 14, 28 (1.28±0.29vs0.10±0.01、0.80±0.07vs0.10±0.01、0.65±0.13vs0.10±0.01) in the PQ group were all upregulated as compared with that of the control group. PlGF mRNA on day 7, 14, 28 in the captopril and Losartan intervention groups were significantly decreased (0.94±0.04、0.71±0.09、0.52±0.24 and 0.80±0.12、0.66±0.11、0.51±0.03) . PlGF positive expression index on day 7, 14, 28 (2.27±0.34 vs0.13±0.01、1.78±0.41 vs0.14±0.03、1.25±0.69 vs0.13±0.01) in the PQ group were all upregulated as compared with that of the control group. PlGF positive expression index on day 7, 14, 28 in the captopril and Losartan treatment groups were significantly decreased (1.53±0.78、1.17±0.79、0.97±0.61 and 1.36±0.63、1.24±0.80、0.83±0.47) . PlGF positive expression index on day 7 in the two intervention groups were significantly decreased, as compared with PQ group (P<0.05) .@*Conclusion@#PlGF may plays an important role in the development of pulmonary fibrosis following paraquat-induced lung injury in rats. Captopril and losartan had an inhibitory effect on paraquat-induced pulmonary fibrosis, and the effect may be due to inhibition of angiotensin II and, in part, be associated with reduction in PlGF.

Significancia del desbalance de los factores angiogénicos en preeclampsia

La participación de los factores antiangiogénicos, la forma soluble de la fms-semejante a la tirosina quinasa (Flt-1s) y la endoglina soluble (Engs), en el desarrollo de la preeclampsia (PE) se ha demostrado en múltiples estudios clínicos y experimentales. Estos estudios están complementados por estudios en animales, en los cuales la sobreexpresión de estos factores antiangiogénicos origina manifestaciones clínicas muy similares a la PE. El origen de esta enfermedad permanece desconocido. Sin embargo, factores genéticos, ambientales e inmunológicos parecen alterar el desarrollo normal de la placenta, lo cual conduce últimamente a la PE. Flt-1s y Engs inhiben la producción y las propiedades proangiogénicas del factor de crecimiento vascular endotelial (FCVE) y del factor de crecimiento placentario (FCP), necesarios para el desarrollo normal vascular de la placenta y las adaptaciones vasculares fisiológicas del embarazo. Cantidades exageradas de Flt-1s y Engs se producen en la placenta disfuncional y se liberan en la circulación materna. Altas concentraciones de Flt-1s y Engs se encuentran en la circulación materna semanas antes de que la enfermedad sea detectada clínicamente. Las capacidades de los factores angiogénicos para predecir PE en embarazos asintomáticos de riesgo bajo y alto son inconsistentes y no útiles para el uso clínico. Por otro lado, proporciones de los factores Flt-1s/FCP, FCP/Flt-1s, y FCP/Eng poseen valores predictivos más altos para diagnosticar PE y predecir sus complicaciones en mujeres con sintomatología de PE. En estas condiciones, el uso clínico de estos marcadores biológicos podría ser implementado en un futuro cercano. Las propiedades biológicas y farmacocinéticas de las estatinas las convierten en uno de los medicamentos con más potencial preventivo para la PE. Otros opciones terapéuticas que se están estudiando son medicamentos que directamente inhiban los factores antiangiogénicos circulantes. Estudios in vitro y estudios pilotos clínicos se están realizando actualmente examinando la seguridad materno-fetal, la transferencia placentaria y la efectividad de estas terapias.

The role of the antiangiogenic factors, the soluble form of the fms-like tyrosine kinase receptor 1 (sFlt1) and the soluble endoglin (sEng), in the development of preeclampsia (PE) has been demonstrated in multiple clinical and experimental studies. These studies are complemented by animal studies, in which overexpression of these antiangiogenic factors leads to clinical manifestations similar to PE. Although, the origin of this disease remains unknown, genetic, environmental, and immunological factors appear to affect the normal placental development, resulting ultimately in PE. sFlt-1 and sEng inhibit the proangiogenic properties of the vascular endothelial growth factor (VEGF) and the placental growth factor (PlGF), affecting the normal vascular development in the placenta and the physiological vascular adaptations that occur in pregnancy. Exaggerated amounts of sFlt-1 and sEng, produced in the dysfunctional placenta, are released into the maternal circulation and elevated circulating concentrations of these antiangiogenic factors are found several weeks prior to the clinical manifestations of the disease. Multiple studies have reported the capacity of circulating antiangiogenic factor concentrations to predict PE in asymptomatic low and high risk pregnancies. The reported predictive values of sFlt-1 and sEng are inconsistent across these studies and therefore their clinical use in this population is not recommended. On the other hand, maternal plasma concentrations of these factors appear to have a better performance in women with symptoms of PE. Among the possible combinations, the ratios of sFlt-1/PlGF, PlGF/sFlt-1, and PlGF/Engs seem to have the highest sensitivities and specificities to diagnose PE as well as the highest predictive values for PE-related adverse outcomes. These properties support their clinical use in this setting and it is likely those ancillary tests will be incorporated to the clinical practice in the near future. The participation of antiangiogenic factors in the pathogenesis of PE, also have stimulated investigation of new targeted therapies. The biological and pharmacokinetic properties of statins have converted them in one of the most promising preventive therapies for this disease. Others are investigating agents that directly inhibit the circulating antiangiogenic factors. In-vitro and pilot clinical studies are currently evaluating the effectiveness, maternal-fetal safety, and placental transference of these therapies.

Research progress in the relationship between VEGF and leukemia / 白血病·淋巴瘤

The levels of multiple vascular endothelial growth factor (VEGF) in patients with hematological malignancies are up-regulated,which associate with disease outcome.VEGF is a major cytokine involved in angiogenesis,and has been related to a variety of functions of endothelial cells.This paper reviews the role of VEGF in leukemia,and discusses the latest development of placenta growth factor in chronic myeloid leukemia.

The discovery of placenta growth factor and its biological activity

Angiogenesis is a complex biological phenomenon crucial for a correct embryonic development and for post-natal growth. In adult life, it is a tightly regulated process confined to the uterus and ovary during the different phases of the menstrual cycle and to the heart and skeletal muscles after prolonged and sustained physical exercise. Conversly, angiogenesis is one of the major pathological changes associated with several complex diseases like cancer, atherosclerosis, arthritis, diabetic retinopathy and age-related macular degeneration. Among the several molecular players involved in angiogenesis, some members of VEGF family, VEGF-A, VEGF-B and placenta growth factor (PlGF), and the related receptors VEGF receptor 1 (VEGFR-1, also known as Flt-1) and VEGF receptor 2 (VEGFR-2, also known as Flk-1 in mice and KDR in human) have a decisive role. In this review, we describe the discovery and molecular characteristics of PlGF, and discuss the biological role of this growth factor in physiological and pathological conditions.

Role of placenta growth factor in cancer and inflammation

Accumulating evidences have documented that angiogenesis is closely linked to inflammation and regulators of angiogenesis play key roles in various inflammatory conditions. PlGF is an angiogenic protein belonging to the VEGF family and is upregulated mainly in pathologic conditions. Recently, PlGF was discovered having a proinflammatory role in inflammatory arthritis and its serum level drew attention not only as a useful surrogate biomarker but also a potential therapeutic target in atherosclerosis and various cancers. Particularly, PlGF has attractive clinical values because endogenous PlGF is redundant for vascular development and physiological vessel maintenance in healthy adults. However, there have been conflicting results about the efficacy of PlGF inhibition depending on the experimental and clinical settings. Further close investigations for resolving the puzzle of PlGF biology are required.

Expression of Placenta Growth Factor in Colorectal Carcinomas

PURPOSE: Placenta growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family. PlGF is implicated in several pathologic processes, including the growth and spread of cancer and tumor angiogenesis. The aim of this study was to evaluate the expression and the clinical implications of PlGF in colorectal cancer. METHODS: In order to ascertain the clinical significance of PlGF expression in colorectal cancer, the researcher analyzed the expression pattern of PlGF by using an immunohistochemical method and attempted to establish if a relationship existed between PlGF expression and microvessel density (MVD), and subsequently between PlGF expression and the predicted prognosis. A total of 83 patients with colorectal cancer were included for immunohistochemical staining. Clinicopathological characteristics were defined according to the tumor-node-metastasis (TNM) criteria of the Union for International Cancer Control. Clinicopathologic factors, such as age, sex, histological types of tumors, tumor cell grade, TNM stage, lymphovascular invasion, and lymph-node metastasis, were reviewed. RESULTS: In this study, the PlGF protein expression level was significantly correlated with MVD, patient survival, and clinicopathological factors such as lymph-node metastasis, TNM staging, lymphatic invasion and vascular invasion. CONCLUSION: PlGF may be an important angiogenic factor in human colorectal cancer, and in this study, PlGF expression level was significantly correlated with positive lymph-node metastases, tumor stage, and patient survival. These findings suggest that PlGF expression correlates with disease progression and may be used as a prognostic marker for colorectal cancer.

The expression of placenta growth factor and IL-6 in placentas with different gestational stages and aging placentas / 中国综合临床

Objective To study the expression of placenta growth factor(PLGF) and IL-6 in placentas with different gestational period.Methods Immunohistochemistry method was used to examine the expression of PLGF and IL-6 in placentas of different normal gestational periods and aging placentas.Results The positive expression rates of IL-6 in the first,second and third trimester of pregnancy were 60.0%(6/10),50/O%(3/6),42.9%(6/14)and 88.9%(8/9),and the positive expression rates of PLGF were 60.0%(6/10),100.O%(6/6),100.O%(14/14)and 55.6%(5/9) respectively.PLGF expression intensity was significantly different among the third trimester of pregnancy placentas,the first trimester of pregnancy placentas (X2=18.89) and the aging placentas (X2=20.42)(P<0.01 for each).IL-6 was significantly different between aging placentas and third trimester of pregnancy placentas(X2=9.47,P<0.05).No statistical significance were found on expression of IL-6 and PLGF among the three trimesters and aging groups (X2=0.625,0,0 and 1.41,respectively,P>0.05).Conclusions The decreasing expression of PLGF in aging placenta tissue illustrates that the PLGF synthesis and secretion is decreased by trophoblast cells but IL-6 expression is remarkably increased,which may play an important role in the pathogenesis of placental senescence.

Expression of Placenta Growth Factor in the Oral Squamous Cell Carcinoma

0.6, P < .05). 2. In the PlGF gene RT-PCR analysis, PlGF expression was more in tumor tissue than in adjacent normal tissue. Paired-samples analysis determined the difference of PlGF mRNA expression level between the cancer tissue and the normal tissue (Student's t - test, P < .05) These findings suggest that up-regulation of the PlGF gene may play a role in progression and local metastasis in invasive oral squamous cell carcinoma.

The pathological role of placenta growth factor / 国际外科学杂志

Angiogenesis is an important step during the occuring, development and metabsis of tumor which is regulated by some factors. PLGF is one of the VEGF family. It is homologous with VEGF-A, VEC,-FR-1 is its receptor. Although it expresses weakly during physiology. PLGF is an important pathologic angio-genesis factor at the condition such as anoxia, truma or tumor. Becanse its expression becomes strong at path-ologic cyophoria and many kinds of tumors, PLGF has a good value in clinic reasereh.

Expression of placenta growth factor mRNA in the rat placenta during mid-late pregnancy

The placenta is an essential organ that synthesizes several growth and angiogenic factors for its own growth as well as fetal development. It is known that the placenta growth factor (PlGF)is a member of the vascular endothelial growth factor family and is critical for placental growth and fetal development. However, there is little information regarding the expression pattern and cellular localization of PlGF mRNA in rat placenta during pregnancy. The aim of this study was to define the distribution of PlGF mRNA in rat placenta at various gestations. RT-PCR analysis showed that the expression level of PlGF mRNA increased as gestation advanced. Using in situ hybridization histochemistry, positive cells of PlGF mRNA were detected in chorionic villi. PlGF mRNA was expressed in the trophoblast cells and stroma cells surrounding the blood vessels within chorionic villi on day 13 and 15. Also, positive signals of PlGF mRNA were strongly detected in stroma cells of chorionic villi on day 17, 19, and 21. In particular, the density and number of positive signals of PlGF mRNA was significantly increased as gestation advanced. The expression pattern of PlGF mRNA in rat placenta during pregnancy demonstrates that PlGF plays a functional role for placental growth and fetal development during mid-late pregnancy.