The study was to investigate the expression of VEGFA, VEGFC, angiopoietin-1, angiopoietin-2 and their receptors on yolk sac blood island, AGM region during gestation of 3th-12th weeks of human embryo. Human embryo contingently aborted at 3 - 12 weeks of gestation were collected with signed agreements of the pregnant women suffered from accidental abortions. The specimens were fixed by 4% paraformaldehyde and embedded by paraffin. 5 micro m serial sections were made. HE and immunohistochemistry method (SABC) and light-microscope were employed. The results showed that VEGFA and its receptors flt1/flk-1, VEGFC and its receptor flt-4, angiopoietin-2 and its receptor tie-2 proteins were expressed strongly and angiopoietin-1 was weakly expressed by hematopoietic cells and vascular endothelial cells of blood island at 21 and 25 days of gestation. In the 4th week of gestation, immuno-positive reaction of these factors and their receptors appeared in the aorta and mesonephros deposited in larger, rounded and nucleated cells which represented hematopoietic cells. Up to 7th week, positive hematopoietic cells in the regions were much abundant. The number of positive cells decreased at 8th week. Up to 12th week, almost all blood cells were immuno-negative. VEGFA, flt-1, flt-4, angiopoietin-1, angiopoietin-2 and Tie-2 protein were expressed mainly by gonad at 6 - 8 weeks, but it did not express VEGFC and flk-1. The immuno-reaction of the factors and their receptors could not detected in vascular endothelial cells during 3-12th weeks of gestation. It is concluded that hematopoietic cells and endothelial cells in blood island of yolk sac, mesonephros and dorsal aorta co-expressed some factors and their receptors in relation to vasculogenesis and hematopoiesis. Intraembryonic hematopoiesis began in the 4th week of gestation.
Angiopoietin-1 ; analysis ; Angiopoietin-2 ; analysis ; Embryo, Mammalian ; chemistry ; Extracellular Matrix Proteins ; analysis ; Humans ; Immunohistochemistry ; Receptor, TIE-2 ; analysis ; Receptors, Vascular Endothelial Growth Factor ; analysis ; Vascular Endothelial Growth Factor A ; analysis ; Vascular Endothelial Growth Factor C ; analysis ; Vascular Endothelial Growth Factor Receptor-1 ; Vascular Endothelial Growth Factor Receptor-2 ; analysis ; Vascular Endothelial Growth Factor Receptor-3 ; analysis ; Yolk Sac ; chemistry

Adult ; Aged ; Endothelial Growth Factors ; analysis ; physiology ; Female ; Humans ; Intercellular Signaling Peptides and Proteins ; analysis ; physiology ; Lymphokines ; analysis ; physiology ; Male ; Middle Aged ; Nasal Polyps ; chemistry ; etiology ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factor Receptor-2 ; analysis ; Vascular Endothelial Growth Factors

OBJECTIVETo explore the role of angiogenesis in bone marrow in acute myeloid leukemia (AML).

METHODSBone marrow culture supernatant was assayed for vascular endothelial growth factor (VEGF) by ELISA, bone marrow biopsies from 28 newly diagnosed AML patients were assayed for microvessel density (MVD), VEGF and its receptors KDR, Flt-1 by immunohistochemical staining before and after induction chemotherapy.

RESULTSCulture supernatant of AML bone marrow mononuclear cells showed higher amount of VEGF (425.31 ng/L) than that of control (140.12 ng/L). The VEGF and KDR expressions and MVD were significantly higher in newly diagnosed AML patients (78.6%, 78.6% and 7.1%, respectively) than that of control group (P < 0.05). There was a positive correlation between VEGF, KDR and MVD. The positive rate of VEGF, KDR and MVD reduced to normal after the patients achieved complete remission, while in non-remission patients did not. Kaplan-Meier analysis showed that the survival time was longer in VEGF negative group than in VEGF positive group. The pre-treatment MVD and VEGF had no correlation with survival time.

CONCLUSIONSThere is remarkable angiogenesis in AML and VEGF/KDR signaling pathway takes an important role in the pathological angiogenesis. VEGF could be used as a prognostic factor in AML.

Adolescent ; Adult ; Aged ; Child ; Female ; Humans ; Leukemia, Myeloid, Acute ; metabolism ; therapy ; Male ; Middle Aged ; Neovascularization, Pathologic ; etiology ; Signal Transduction ; Vascular Endothelial Growth Factor A ; analysis ; physiology ; Vascular Endothelial Growth Factor Receptor-1 ; analysis ; Vascular Endothelial Growth Factor Receptor-2 ; analysis

The aim was to study the expression of VEGF-A, VEGF-C, angiopoietin-1, angiopoietin-2 and their receptors on development liver during gestation of weeks 3-12 of human embryo. Human embryo contingently aborted at 3-12 weeks of gestation were collected with signed agreements of the pregnant women suffered from accidental abortions. The specimens were fixed by 4% paraformaldehyde and embedded by paraffin. 5 microm serial sections were made. HE staining, immunohistochemistry method and light-microscope were employed. The results showed that at 4-5 weeks of development, liver was constituted by a few hepatic cords. Hematopoietic cell or blood cells were undetectable in the 4 week of gestation. A few cells which were larger, rounded and nucleared cells appeared and expressed VEGFA, flt-4 and Tie-2 proteins strongly in liver at 5 weeks of gestation. The number of these immuno-positive cells was highest in the 7th week and decreased at 11-12 weeks of gestation. These cells expressed flk-1 transiently in the 6th week. VEGF-C and flt-1 were expressed by hepatic cells from weeks 7 to 12 of gestation. The immuno-positive products were deposited in plasma of hepatic cells. Angiopoietin-1, angiopoietin-2 and Tie-2 were detectable on those cells which expressed VEGFA, flt-4 and Tie-2 from weeks 5 to 12 of gestation. The expression of angiopoietin-1 and angiopoietin-2 were weakly and Tie-2 was strongly. They were expressed weakly too by hepatic cells at 5 to 12 weeks of gestation. All factors and their receptors were undetectable on vascular endothelial cells at 4-12 weeks of gestation. It is concluded that the expression patterns of VEGF family on cells of liver are different before and after 7 weeks of gestation. The hematopoiesis in fetal liver may be related to development of hepatic cell.
Angiopoietin-1 ; analysis ; Angiopoietin-2 ; analysis ; Extracellular Matrix Proteins ; analysis ; Female ; Gestational Age ; Humans ; Immunohistochemistry ; Liver ; chemistry ; embryology ; Pregnancy ; Receptor, TIE-2 ; analysis ; Vascular Endothelial Growth Factor A ; analysis ; Vascular Endothelial Growth Factor C ; analysis ; Vascular Endothelial Growth Factor Receptor-1 ; Vascular Endothelial Growth Factor Receptor-3 ; analysis

Placental development requires extensive angiogenesis and the invasion of the maternal decidua by the trophoblasts. Adequate and organized interaction of vascular endothelial growth factors (VEGF), placenta growth factors (PlGF), and their receptors are essential for a normal development and function of the placenta. In this study, we evaluated the expressions of PlGFs and their receptors, mRNAs by Northern blotting, in situ hybridization and RT-PCR in the normal and pregnancy-induced hypertensive (PIH) placentas. The expression level of PlGF-2 mRNA was lower in the PIH placentas compared to control as assessed by Northern blotting and in situ hybridization. PlGF mRNA was mainly localized to the vasculosyncytial membrane of placental villi and villous stroma. The expression of PlGF receptor-1 (PlGFR-1) was significantly increased in the PIH placentas compared to the normal ones. These results suggest that the alteration of PlGF-2 and PlGFR-1 mRNA expressions in the placenta are related to the pathogenesis of PIH.
Female ; Gene Expression ; Human ; Hypertension/*physiopathology ; In Situ Hybridization ; Placenta/*physiology ; Pre-Eclampsia/*physiopathology ; Pregnancy ; Pregnancy Proteins/*genetics ; RNA, Messenger/analysis ; Vascular Endothelial Growth Factor A/*genetics ; Vascular Endothelial Growth Factor Receptor-1/genetics ; Vascular Endothelial Growth Factor Receptor-2/genetics

BACKGROUNDAfter myocardial infarction, specific growth factors promote cardiac angiogenisis, leading to a therapeutic effect. Although this effect is mediated by specific receptors in the endothelium of the cardiac microvasculature, few studies have investigated dynamic changes in their expression. We explored this phenomenon in a murine model.

METHODSWe observed the mRNA expression of receptors by specific angiogenesis gene microarray at day 3 and day 7 after infarction. The vascular endothelial growth factor (VEGF) receptor Flk-1 was observed at the protein level at day 3 and day 7 by immunohistochemistry. The dynamic expression of fibroblast growth factor receptor-1 (FGFR-1) mRNA in the border zone and the noninfarcted zone at day 3, day 7, day 14, and day 42 was investigated by real-time PCR. Statistical significance was analyzed with SPSS 10.0 software using one-way analysis of variance (ANOVA).

RESULTSThree days after infarction, 9 receptors in the border zone and 7 receptors in the noninfarcted zone were down-regulated. Two receptors in the infarct edge and 5 receptors in the distant myocardium were up-regulated. However, at day 7, 11 receptors in the border zone were up-regulated, and only one was down-regulated. In the border zone, Flk-1 levels decreased at day 3 but increased significantly at day 7. Real-time PCR showed that FGFR-1 mRNA decreased markedly in the border zone at day 3 but increased afterward for at least 6 weeks. In the early stage (3 days) after infarction, the expression of receptors had decreased to some extent. However, at day 7, receptor expression was active and had moved from the distant noninfarcted zone to the border zone as a part of the acute repair process.

CONCLUSIONSelecting the proper growth factors to target receptors with protective activity, and determining appropriate therapeutic timing may be important to the success of therapeutic angiogenesis.

Animals ; Endothelium, Vascular ; metabolism ; Male ; Microcirculation ; Myocardial Infarction ; metabolism ; Myocardium ; metabolism ; Oligonucleotide Array Sequence Analysis ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Receptor, Fibroblast Growth Factor, Type 1 ; genetics ; Vascular Endothelial Growth Factor Receptor-2 ; analysis

OBJECTIVETo study the difference in the expression of VEGF, bFGF and their receptors between young and postmenopausal women with breast cancer.

METHODSThe expression of VEGF, FLK-1, bFGF and FLG in 40 young and 30 postmenopausal women with breast cancer was studied by immunohistochemical method (SABC), with its relation with axillary lymph node metastasis and the clinical and pathologic characteristics. The expression index between these two groups was compared.

RESULTSThe positive axillary lymph node rate and the mean expression of VEGF, bFGF in the young group were higher than postmenopausal group (P < 0.01 and P < 0.05), respectively. The mean expression of VEGF, bFGF, FLK-1 and FLG of axillary lymph node positive patients was higher than the negative ones both in young and postmenopausal women groups (P < 0.05 and P < 0.01). There was also a significant difference in VEGF, bFGF, FLK-1, FLG and MVC between the stage 0 - II and stage III - IV (P < 0.05 and P < 0.01) in both groups.

CONCLUSIONBreast cancer angiogenesis, characterized by the high expression of VEGF and bFGF, is directly correlated with the high tumor aggressiveness in the young women.

Adult ; Age Factors ; Aged ; Breast Neoplasms ; chemistry ; pathology ; Female ; Fibroblast Growth Factor 2 ; analysis ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Middle Aged ; Postmenopause ; Receptor, Fibroblast Growth Factor, Type 1 ; analysis ; Receptors, Estrogen ; analysis ; Vascular Endothelial Growth Factor A ; analysis ; Vascular Endothelial Growth Factor Receptor-2 ; analysis

OBJECTIVETo study the effects of prolonged 75% oxygen exposure on the expression of vascular endothelial growth factor (VEGF) and its receptors (VEGFR1 and VEGFR2) in the neonatal rat lungs and to elucidate the effects of prolonged exposure of high concentration of oxygen on lung vascular development and its relationship with bronchopulmonary dysplasia (BPD).

METHODSForty eight Sprague-Dawley rat pups were randomly exposed to air (control group) and 75% oxygen (experimental group) 12 hrs after birth. The rats were sacrificed 7, 14 and 21 days after exposure and their lungs were sampled. The lung sections were stained with hematoxylin and eosin for histological evaluation. Expression of VEGF, VEGFR1 and VEGFR2 protein and mRNA was detected by immunohistochemistry and RT-PCR.

RESULTSAfter being exposed to 75% oxygen for 21 days, lung tissues had pathological changes as 'new' BPD. Expressions of VEGF protein (10.9 + or - 2.7 vs 30.8 + or - 6.4), VEGFR1 protein (5.4 + or - 1.4 vs 15.6 + or - 3.4) and VEGFR2 protein (11.3 + or - 2.6 vs 21.7 + or - 4.5) on day 21 in the experimental group decreased significantly as compared with the control group (p<0.05). The expression of VEGF mRNA (1.6 vs 3.3), VEGFR1 mRNA (0.4 vs 6.6) and VEGFR2 mRNA (0.5 vs 4.9) on day 21 in the experimental group also decreased significantly as compared with the control group (p<0.05).

CONCLUSIONSProlonged exposure of high concentration of oxygen may cause BPD possibly by inhibiting lung vascular development in neonatal rats.

Animals ; Animals, Newborn ; Bronchopulmonary Dysplasia ; etiology ; Female ; Humans ; Infant, Newborn ; Lung ; blood supply ; Male ; Oxygen ; toxicity ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Vascular Endothelial Growth Factor A ; analysis ; genetics ; Vascular Endothelial Growth Factor Receptor-1 ; analysis ; genetics ; Vascular Endothelial Growth Factor Receptor-2 ; analysis ; genetics

BR55 is an ultrasound contrast agent targeting vascular endothelial growth factor receptor 2,which can be used to detect tumor neovascularization and improve the diagnostic accuracy.Overseas researchers have used BR55 for human ultrasound molecular imaging,which showed good safety and tolerance.We reviewed the research progress on BR55 applied in the evaluation of tumor neovascularization from the composition,characteristics,animal experiments,and clinical studies of BR55.
Animals ; Contrast Media ; Humans ; Microbubbles ; Molecular Imaging/methods* ; Neovascularization, Pathologic/diagnostic imaging* ; Ultrasonography/methods* ; Vascular Endothelial Growth Factor Receptor-2/analysis*

OBJECTIVETo investigate the expression and pattern of vascular endothelial growth factor (VEGF) and its fetal liver kinase-1 (Flk-1) receptor in spinal cord and dorsal root ganglia after neurotomy of sciatic nerve in rats.

METHODSForty-five adult male Wistar rats were divided randomly into a control group (n=5) and an experimental group (n=40). The bilateral sciatic nerves of the rats in the experimental group underwent neurotomy and the L4-L6 spinal cord and the corresponding dorsal root ganglia were harvested respectively at 8 hours, and 1, 3, 5, 7, 10, 14 and 21 days (8 subgroups with 5 rats each) after operation. The rats in the control group only underwent an exposure of sciatic nerve without neurotomy. Immunohistochemistry and image analysis were used to study the expression of VEGF and its Flk-1 receptor.

RESULTSBoth VEGF and Flk-1 receptor expressed in the normal rat spinal cord and dorsal root ganglia. In response to neurotomy, their expression reached a higher level and persisted for a short time then declined to the normal level rapidly. Besides, positive staining of Flk-1 was observed in both glial cells and nerve fibers, which located in the white matter of the spinal cord.

CONCLUSIONSVEGF can promote the regeneration of peripheral nerves from the angle of central neurons, which establishes the experimental and theoretical foundation for VEGF treating peripheral nerve injuries.

Analysis of Variance ; Animals ; Ganglia, Spinal ; metabolism ; Immunoenzyme Techniques ; Male ; Random Allocation ; Rats ; Rats, Wistar ; Sciatic Nerve ; metabolism ; surgery ; Vascular Endothelial Growth Factor Receptor-2 ; biosynthesis ; Vascular Endothelial Growth Factors ; biosynthesis