Vascular endothelial growth factor (VEGF) exerts its biological functions by its specific VEGF receptors (VEGFRs), which includes VEGFR-1, VEGFR-2, VEGFR-3, neuropilin-1 and neuropilin-2. These VEGF receptors not only distribute in endothelial cells, but also in epidermal keratinocytes. VEGFRs may play a significant role in pathogenesis of the epidermal neoplasm and the VEGF-VEGFR signaling pathway may be a novel therapy target for neoplasm derived from epidermis.
Animals ; Epidermis ; metabolism ; Humans ; Neoplasms ; metabolism ; Neuropilins ; genetics ; metabolism ; Receptors, Vascular Endothelial Growth Factor ; genetics ; metabolism ; Vascular Endothelial Growth Factor Receptor-1 ; genetics ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; genetics ; metabolism ; Vascular Endothelial Growth Factor Receptor-3 ; genetics ; metabolism

OBJECTIVETo observe the expression levels of hippocampal vascular endothelial growth factor (VEGF), fms-like tyrosine kinase-1 (flt-1), basic fibroblast growth factor (bFGF), and basic fibroblast growth factor receptor (bFGF-r) in vascular dementia (VD) rats, thus studying the angiogenesis mechanism of moxibustion in VD.

METHODSSixty male elderly Wistar rats were selected. The VD rat model was prepared by bilateral carotid artery occlusion and reperfusion of sodium nitroprusside injection. The model rats were divided into 3 groups by the random digit table, i. e., the moxibustion group, the Western medicine group, and the model group. A sham-operation control group was also set up. In the moxibustion group rats was acupunctured at Baihui (GV20), Shenting (GV14), and Dazhui (GV24). Aniracetam was given to rats in the Western medicine group by gastrogavage for 2 therapeutic courses, 15 days as one course. The learning and memory results were observed by the neuroethological score in combination of step-down avoidance test before treatment and by the end of the 2nd course respectively. The expression levels of hippocampal VEGF, flt-1, bFGF, and bFGF-r of all rats were detected using immunohistochemical assay.

RESULTSAfter 2 courses of treatment, statistical difference existed in the latent period, the error times, and the neuroethological score in the moxibustion group and the Western medicine group when compared with the model group (P < 0.01, P < 0.05). Statistical difference existed in the latent period and the neuroethological score between the moxibustion group and the Western medicine group (P < 0.05), which indicated that moxibustion and Western medicine showed significant effects in improving the latent period, decreasing the error times and the neuroethological score. Better results were obtained in the moxibustion group than in the Western medicine group (P < 0.01, P < 0.05). Statistical difference of the average grey level (AGL) of hippocampal VEGF, flt-1, and bFGF existed in the moxibustion group and the Western medicine group when compared with the model group. Statistical difference of the bFGF-r expression existed only between the moxibustion group and the model group. Statistical difference of the VEGF and flt-1 expressions existed between the moxibustion group and the Western medicine group (P < 0.05).

CONCLUSIONSMoxibustion showed confirmative effects in improving the behavioral score and memory performance in VD rats. Its mechanisms might lie in that moxibustion regulated and controlled the expression levels of hippocampal VEGF, flt-1, bFGF, and bFGF-r in VD rats. Particularly it up-regulated the expression levels of key factors VEGF and flt-1, promoted the angiogenesis in the vital parts, and ultimately stimulated the repairing mechanisms of cerebral nerve injury.

Animals ; Dementia, Vascular ; metabolism ; therapy ; Fibroblast Growth Factor 2 ; metabolism ; Hippocampus ; metabolism ; Male ; Moxibustion ; Rats ; Rats, Wistar ; Receptor, Fibroblast Growth Factor, Type 2 ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-1 ; metabolism

OBJECTIVEThe effect of vascular endothelial growth factor(165) (VEGF(165)) on intracellular free magnesium ([Mg(2+)](i)) and the relationship between Mg(2+) and angiogenesis in human umbilical vein endothelial cells (HUVECs) were investigated in this study.

METHODS[Mg(2+)](i) in HUVECs loaded with fluorescent magnesium indicator mag-fura-2 were quantitatively detected with the use of intracellular cation measurement system. HUVECs were obtained from normal fetus and cultured in M199 with 0.2 fetal bovine serum. The angiogenesis effects of VEGF(165) were observed in presence of 0 mmol/L, 1 mmol/L or 2 mmol/L of extracellular Mg(2+).

RESULTSVEGF(165) significantly increased [Mg(2+)](i) in a dose-dependent manner independent of extracellular Mg(2+), Na(+) and Ca(2+) and this effect could be blocked by pretreatment with VEGF(165) receptor-2 (KDR) inhibitor (SU1498). The angiogenesis induced by VEGF(165) was significantly inhibited cells with 0 mmol/L extracellular Mg(2+), the angiogenesis effects of VEGF(165) were similar in cells with 1 mmol/L and 2 mmol/L extracellular Mg(2+) and these effects could be blocked by SU1498.

CONCLUSIONSThese results suggest that the [Mg(2+)](i) increase induced by VEGF(165) originates from intracellular Mg(2+) pools and promotes angiogenesis via KDR-dependent signaling pathways.

Cations, Divalent ; Cells, Cultured ; Endothelial Cells ; metabolism ; Humans ; Magnesium ; metabolism ; Neovascularization, Physiologic ; Signal Transduction ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism

OBJECTIVETo study the expression of vascular endothelial growth factor (VEGF) and its receptors, the fms-like tyrosine-1 (flt-1) and kinase insert domain-containing receptor (KDR) in endometrial carcinoma and investigate the functions of VEGF and its receptors for endometrial carcinoma angiogenesis and its relation to the grade of tumor.

METHODSImmunocytochemistry and in situ hybridization technique were used to measure the level of VEGF, flt-1, KDR protein and mRNA in endometrial carcinoma tissue from 23 patients and endometrial samples from 6 normal menopausal women. A few endometrial carcinoma samples were homogenized for Western blot analysis. The blood vessel density was estimated by counting blood vessels stained with endothelial marker VIII factor.

RESULTSThe VEGF and its receptors were widely expressed in the cytoplasm of endothelial cells and tumor cells of endometrial carcinoma. The level of VEGF protein in endothelial cells and endometrial cancer cells of grade II and III tumor tissues was higher than that in grade I and normal menopausal endometrium (P < 0.05). VEGF mRNA did not show higher expression with the increase of tumor grade but its expression in normal tissue was lower than that in cancer (P < 0.05). The expression of flt-1 protein and mRNA in endothelial cells got higher in III than in grade II and I (P < 0.05), but invariable in cancer cells (P > 0.05), flt-1 expression in cancer was higher than that in normal menopausal endometrium either in endothelial cells or in cancer cells (P < 0.05). The expression of KDR protein in endothelial and cancer cell was high but did not alter with the increase of tumor grade (P > 0.05), the level of its mRNA was higher in cancer than that in normal tissue (P < 0.05). The microvascular density in grade III (48 +/- 12) was higher than that in grade II (26 +/- 16), grade I (27 +/- 14) and normal menopausal tissue (26 +/- 11, P < 0.05).

CONCLUSIONSThe expression pattern of VEGF, flt-1 and KDR protein and mRNA increased with the increase of tumor grade in endometrial carcinoma indicates that VEGF and its receptors contribute to the neovascularization of tumors and is one of the factors that relate to rapid tumor growth of endometrial carcinoma.

Endometrial Neoplasms ; metabolism ; physiopathology ; Endothelial Growth Factors ; genetics ; metabolism ; Extracellular Matrix Proteins ; metabolism ; Female ; Gene Expression ; Humans ; Intercellular Signaling Peptides and Proteins ; genetics ; metabolism ; Lymphokines ; genetics ; metabolism ; Neovascularization, Pathologic ; RNA, Messenger ; metabolism ; Receptors, Vascular Endothelial Growth Factor ; genetics ; metabolism ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factor Receptor-1 ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism ; Vascular Endothelial Growth Factors

OBJECTIVETo observe the effect of Panax notoginseng (PN) on pathological features in chronic subdural hematoma (CSDH) rabbits and its mechanisms.

METHODSA stable pathological animal model similar to CSDH in humans could be established using subdural injections of small number of blood through a subdural pre-catheter in rabbits. After successful modeling, 18 rabbits were randomly divided into the model group, the low dose PN group (0.125 g/kg), and the high dose PN group (0.250 g/kg), 6 in each group. Normal saline was given to rabbits in the model group, while PN power was given to those in the PN groups by gastrogavage for 6 successive days. Pathologic features of the hematoma outer membrane were observed by HE staining. The activity of SOD and the content of MDA in the hematoma outer membrane were examined by the colorimetric method. Expressions of CD31, CD34, and VEGF in the hematoma outer membrane were observed by immunohistochemical assay. Expressions of VEGF in the peripheral blood and the subdural hematoma were detected by enzyme-linked immunosorbent assay (ELISA). Expressions of VEGFR-1 and VEGFR-2 in the hematoma outer membrane were detected by Western blot.

RESULTSCompared with the model group, the inflammatory reaction was comparatively lessen and the proliferation of the fibrous tissue was relatively mature in the low and high dose PN groups. The activity of SOD increased (P < 0.05); expressions of CD31 and CD34 were reduced (P < 0.01); VEGF expression in the residual hematoma fluid decreased (P < 0.05) in the high dose PN group. Expressions of VEGF and VEGFR-2 were all reduced in the high and low dose PN groups (P < 0. 05, P < 0.01). Compared with the low dose PN group, expressions of CD31 and CD34 were reduced (P < 0.01), and the VEGFR-2 expression was also reduced (P < 0.05) in the high dose PN group.

CONCLUSIONSPN could promote the fibrous repairing of subdural hematoma in CSDH rabbits. It also lessened inflammation and oxidative injury of the hematoma outer membrane and reduced expressions of VEGF. The pathological angiogenesis could be reduced through influencing VEGFR-2 receptor pathways, which might be an important mechanism.

Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Hematoma, Subdural, Chronic ; metabolism ; pathology ; Panax notoginseng ; chemistry ; Rabbits ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-1 ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism

Endothelial cells that form the inner layers of both blood and lymphatic vessels are important components of the vascular system and are involved in the pathogenesis of vascular and lymphatic diseases. Angiopoietin (Ang)-Tie axis in endothelial cells is the second endothelium-specific ligand-receptor signaling system necessary for embryonic cardiovascular and lymphatic development in addition to the vascular endothelial growth factor receptor pathway. The Ang-Tie axis also maintains vascular homeostasis by regulating postnatal angiogenesis, vessel remodeling, vascular permeability, and inflammation. Therefore, the dysfunction of this system leads to many vascular and lymphatic diseases. In light of the recent advances on the role of the Ang-Tie axis in vascular and lymphatic system-related diseases, this review summarizes the functions of the Ang-Tie axis in inflammation-induced vascular permeability, vascular remodeling, ocular angiogenesis, shear stress response, atherosclerosis, tumor angiogenesis, and metastasis. Moreover, this review summarizes the relevant therapeutic antibodies, recombinant proteins, and small molecular drugs associated with the Ang-Tie axis.
Angiopoietins ; Endothelial Cells/metabolism* ; Humans ; Lymphatic Diseases ; Lymphatic System/metabolism* ; Receptor, TIE-2/metabolism* ; Signal Transduction ; Vascular Endothelial Growth Factor A

OBJECTIVETo study the expression and distribution of KDR, VEGF and CD34 in yolk sac and liver of human embryo at different development stage.

METHODSYolk sacs and livers of 15 human embryos were analyzed by the immunohistochemical SP kits for the expression of KDR, VEGF and CD34.

RESULTSKDR, VEGF and CD34 were all expressed in yolk sacs and livers of the embryos. In the intermediate liver group, the grey value of KDR and VEGF were 103.8 +/- 6.1 and 96.4 +/- 6.3, respectively, stronger than that in the late liver group which were 90.4 +/- 6.0 and 87.4 +/- 6.3, respectively (P < 0.05). A positive correlation between the levels of KDR and VEGF was observed (P < 0.05).

CONCLUSIONThe expression of KDR and CD34 in yolk sac and liver of embryo suggests the presence of hemangioblast in these organs. Interaction of KDR and VEGF might relate to survival, proliferation, migration and differentiation of hemangioblasts.

Embryo, Mammalian ; metabolism ; Humans ; Immunohistochemistry ; Liver ; embryology ; metabolism ; Vascular Endothelial Growth Factor A ; biosynthesis ; Vascular Endothelial Growth Factor Receptor-2 ; biosynthesis ; Yolk Sac ; metabolism

OBJECTIVETo investigate the correlation between the expression of the kinase insert domain-containing receptor (KDR) and the histological grade of prostate adenocarcinoma.

METHODSForty-eight samples of prostate adenocarcinoma tissues and 20 samples of benign prostatic hypertrophy (BPH) tissues were studied by LsAB immunohistochemical staining.

RESULTSThe positive expression rate of KDR was 73% in prostate adenocarcinoma and 30% in BPH. The expression of KDR was stronger in prostate adenocarcinoma, and there was no relationship between staining intensity and the histological grade of carcinoma.

CONCLUSIONKDR, expressed more highly in prostate adenocarcinoma, promises to be a new target in the treatment of prostate adenocarcinoma.

Adenocarcinoma ; metabolism ; Humans ; Male ; Prostatic Hyperplasia ; metabolism ; Prostatic Neoplasms ; metabolism ; Receptors, Vascular Endothelial Growth Factor ; biosynthesis ; Vascular Endothelial Growth Factor Receptor-2 ; biosynthesis

The objective of study was to explore the role of vascular endothelial growth factor (VEGF) and its receptor-2 in pathogenesis of acute myeloid leukemia. The acute myeloid leukemia model was established on 20 mice with severe combined immunodeficiency (SCID) transplanted by HL-60 cells. The mice were divided into the normal control and test group randomly. The expression of VEGF was detected by enzyme linked immunosorbent assay (ELISA). The expression of VEGFR-2 mRNA was detected by RT-PCR. The results showed that the establishment of acute myeloid leukemia model was succeeded on all SCID mice by HL-60 cell transplantation. The expressions of VEGF and VEGFR-2 mRNAs could be determined on all mice. As compared with the normal control group, the expressions of VEGF and VEGFR-2 mRNAs in the test group significantly increased, but gradually increased during the course of disease. It is concluded that the abnormal expressions of VEGF and VEGFR-2 exist in mice with acute myeloid leukemia, which may be involved in the pathogenesis of AML.
Animals ; Bone Marrow ; pathology ; HL-60 Cells ; Humans ; Mice ; Mice, SCID ; Neoplasm Transplantation ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism

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