Vascular Endothelial Growth Factor (VEGF) is a potent angiogenic factor with a key role in several pathological processes, including wound repair as well as a effective vascular permeability factor. This article review the present study of VEGF in molecular biology, the connection with repair and expression regulation and so on.
Animals ; Endothelial Growth Factors/physiology* ; Forensic Medicine ; Humans ; Intercellular Signaling Peptides and Proteins/physiology* ; Lymphokines/physiology* ; Rats ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors ; Wound Healing/physiology*

The purpose of this preliminary study is to elucidate that vascular endothelial growth factor (VEGF) influences contrast enhancement of hepatic tumors on computed tomography (CT). Fourteen patients with hepatic tumors (11 hepatocellular carcinomas; 3 metastatic cancers) underwent a dual-phase dynamic helical CT or computed tomographic hepatic arteriography. The attenuation of each mass was determined as hyperattenuation, isoattenuation or hypoattenuation with respect to the adjacent nontumorous parenchyma. Gun-needle biopsy was done for each tumor, and paraffin sections were immunostained with anti- VEGF antibody by the avidin-biotin-peroxidase complex method. The pathologic grade was made by intensity (1 +, 2+, 3+) and area (+/-, 1 +, 2+). The tumor ranged 2.0-14.0 cm in size (mean, 5.8 cm). In arterial phase, the intensity was not correlated with the degree of enhancement (p=0.086). However, the correlation between the attenuation value of hepatic arterial phase and the area of positive tumor cells was statistically significant (p=0.002). VEGF may be the factor that enhances the hepatic mass with water-soluble iodinated contrast agent in CT.
Adult ; Aged ; Capillary Permeability ; Endothelial Growth Factors/physiology* ; Endothelial Growth Factors/analysis ; Female ; Human ; Liver Neoplasms/radiography* ; Liver Neoplasms/blood supply ; Lymphokines/physiology* ; Lymphokines/analysis ; Male ; Middle Age ; Prospective Studies ; Radiographic Image Enhancement* ; Tomography, X-Ray Computed

OBJECTIVETo investigate the value of application of recombinant human VEGF to accelerate flap viability in a rat model of non-ischemic prefabricated flap.

METHODSPrefabricated Flaps were created in 48 SD rats. An autologous tail artery loop was anastomosed to the femoral artery and vein, and implanted subcutaneously in the lower abdomen. Flaps were divided into four groups of 12 each. At the time of loop implantation, the control groups received 0.9% NaCl (Control 1) and 16% (V/W) polyvinyl alcohol (PVA) solution (Control 2). The treatment groups received VEGF in 0.9% NaCl (treatment 1) and VEGF in PVA (treatment 2). In each group, a 3 cm x 4 cm flap nurtured by the tail artery pedicle was elevated and resutured into place after 3, 4 and 5 weeks. The percentage of surviving skin of each flap was determined by planimetry 7 days after flap elevation.

RESULTSMean skin survival areas at 3, 4, and 5 weeks were 1%, 0%, 10% in control; 0%, 16%, 25% in control 2; 3.57%, 39.13%, 75.00% in treatment 1; 8.13%, 41.98%, 58.41% in treatment 2. VEGF significantly improved flap survival by 5 weeks (P < 0.05).

CONCLUSIONThese results suggest VEGF can accelerate maturation of prefabricated flaps.

Animals ; Endothelial Growth Factors ; pharmacology ; Female ; Lymphokines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; pharmacology ; Surgical Flaps ; physiology ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors

OBJECTIVEGene therapy has been becoming one of the most attractive medical areas. But the using of gene therapy in plastic surgery is relatively scarce. Our purpose was to investigate the effect of naked plasmid encoding Vascular Endothelial Growth Factor on the viability of the random skin flap by directly injected subcutaneously.

METHODS30 female Sprague-Dawley rats randomly divided into three groups. A random dorsal skin flap of 3 cm x 9 cm was elevated in each of the rats. And 1 ml double-distilled water solution was injected subcutaneously, which was only water in group 1 during the operation, 200 micrograms VEGF cDNA plasmid in group 2 during the operation, 200 micrograms pcDNA3.1/zeo(+)--VEGF in group 3, 24 hours before the operation, respectively. 7 days after the operation, all the animals were sacrificed by overdose anesthetic. The survival tissue was measured with planimetry. Two samples were harvested from each group for pathological check and immunohistochemical test.

RESULTSImmunohistochemical staining demonstrated that there was human VEGF deposited around the capillary in the flaps treated with VEGF gene. The flaps treated with VEGF gene had a larger percentage of survival skin (group 1 = 47% +/- 5.4%, group 2 = 65.4% +/- 6.3%, group 3 = 72.3% +/- 8.5%, P < 0.05).

CONCLUSIONVEGF gene directly injected into subcutaneous can express VEGF. It makes the gene therapy simple and practical and will be promising future in the tissue transplantation.

Animals ; Endothelial Growth Factors ; genetics ; Female ; Genetic Therapy ; Injections, Subcutaneous ; Lymphokines ; genetics ; Rats ; Rats, Sprague-Dawley ; Surgical Flaps ; physiology ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors

OBJECTIVETo investigate the effect of phVEGF165 transfer on vascular remodelling after balloon injury and its possible mechanisms.

METHODS90 New Zealand white rabbits were divided randomly into 3 groups: group I (balloon injury group), group II (pAdtrackCMV group) and group III (pAdtrackCMV-VEGF165 group). All animals were given hypercholesterol diet for 7 days before experiment and continued to receive hypercholesterol diet until being killed. Each group was further divided into five subgroups according to the sacrifice time (3 days, 1, 2, 4 and 8 weeks after transfection). Blood samples and arteries were harvested for further analysis.

RESULTSAt the end of 2 weeks, areas of neointima plus media of group III were smaller than those of group I and II (P < 0.05). The areas under external elastic membrane were larger in group III at 4 weeks and lumen stenosis rates were significantly lower than group I and II (P < 0.05 or 0.01). In group III, VEGF165, metalloproteinases (MMPs) -1, -2, -9 and their tissue inhibitors (TIMPs) 1, 2 could be detected from 3 days after gene transfer and reached the highest level at 2 weeks time and could not be detected by 8 weeks time. In groups I and II, MMP-2 and TIMP-1, -2 could be detected during the whole procedure and the value of TIMP1/MMP1 was significantly higher than in group III (P < 0.01).

CONCLUSIONRemodelling is the main reason for restenosis (RS) after vascular balloon injury. Local pAdtrackCMV-VEGF165 transfer can specifically change the expression of MMPs and facilitate the positive remodelling process, hence, inhibiting restenosis.

Angioplasty, Balloon ; adverse effects ; Animals ; Coronary Restenosis ; etiology ; pathology ; Endothelial Growth Factors ; genetics ; physiology ; Intercellular Signaling Peptides and Proteins ; genetics ; physiology ; Lymphokines ; genetics ; physiology ; Male ; Matrix Metalloproteinases ; metabolism ; Rabbits ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors

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

Angiogenesis is a necessary step in tumor progression, and it correlates an unfavorable prognosis. In multiple myeloma, bone marrow microvessel density and angiogenesis grading correlated with plasma cell labeling index and are poor survival predictors, but the study of myeloma's angiogenesis is very rare. This article was to study the effect of multiple myeloma cell line conditioned media on the proliferation, migration and angiogenesis of human bone marrow endothelial cells (HBMEC). The multiple myeloma cell line conditioned media were obtained by using RPMI 1640 media containing 2% fetal bovine serum (FBS) to cultivate myeloma cell lines for 18 hours. Proliferation and migration of HBMEC were detected by using those media to cultivate HBMEC. Capillary tube formation was performed by using microcarriers cytodex-3 covered with HBMEC in three-dimensional fibrin matrices. The results showed that myeloma conditioned media induced HBMEC's proliferation and migration (P < 0.001), and those media induced capillary tube formation (length and width) of HBMEC (P < 0.001). It was concluded that myeloma cell lines induce HBMEC's proliferation, migration, and capillary tube formation by secreting several cytokines.
Bone Marrow Cells ; cytology ; Cell Division ; Cell Movement ; Endothelial Growth Factors ; analysis ; physiology ; Humans ; Intercellular Signaling Peptides and Proteins ; analysis ; physiology ; Lymphokines ; analysis ; physiology ; Multiple Myeloma ; blood supply ; chemistry ; pathology ; Neovascularization, Pathologic ; etiology ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors

To investigate the role of angiogenesis in multiple myeloma (MM), bone marrow biopsy from 75 adults with newly diagnosed, untreated MM were evaluated. Microvessels were scored in at least 3 areas ( x 200 fields) of the highest microvessel density in representative sections of each bone marrow specimen using immunohistochemistry for CD34. Prognostic variables were also evaluated for the overall survival. Microvessel counts were significantly higher in patients with MM (n=69.42+/-9.67), compared with control (n=26.81+/-2.85). Microvessel density had a weak correlation with percentage of bone marrow plasma cells. By univariate analysis, age, beta2-microglobulin, serum albumin, serum creatinine, serum calcium, hemoglobin, platelet count, and bone marrow plasma cell percentage were correlated with survival. By multivariate analysis, age, serum albumin, serum creatinine, hemoglobin, platelet count and bone marrow plasma cell percentage were correlated with overall survival, whereas microvessel density was not. In summary, microvessel density in bone marrow of MM is significantly increased compared to control, but was not correlated with overall survival. Further studies regarding angiogeneic molecules are needed to determine the functional role of angiogenesis in MM.
Adult ; Aged ; Aged, 80 and over ; Bone Marrow/blood supply ; Endothelial Growth Factors/physiology ; Female ; Hematopoietic Stem Cell Transplantation ; Human ; Lymphokines/physiology ; Male ; Microcirculation ; Middle Age ; Multiple Myeloma/therapy ; Multiple Myeloma/mortality ; Multiple Myeloma/blood supply* ; Neovascularization, Pathologic/physiopathology* ; Survival Rate

OBJECTIVETo investigate the feasibility of endothelialization of bioprosthesis by transfer of vascular endothelial growth factor (VEGF) gene.

METHODSBovine pericardium treated with glutaraldehyde and L-glutamic acid was positioned into the pig right atrium. pcD(2)/hVEGF(121) gene (1 mg) was transferred into the right ventricular myocardium using surgical sutures Reverse transcri ption polymerase chain reaction (RT PCR) was employed to evaluate the expression of myocardial VEGF mRNA. The determination of concentrations of VEGF protein in blood from both the right atrium and peripheral vein, and histological and ultrastructural analysis of implanted bovine pericardium were completed simultaneously.

RESULTSThe concentration of VEGF derived from the right atrium in pcD(2)/hVEGF(121) group was significantly higher than that in the pcD(2) group 10 days after VEGF gene transfer (P < 0.01). The expression of myocardial VEGF mRNA in pcD(2)/hVEGF(121) group was much higher in comparison with that in the pcD(2) group. The morphological analysis demonstrated that the coverage rate of host endothelium in the pcD(2)/hVEGF(121) group was 2.6 times as fast as that in the pcD(2) group at 16 days after VEGF(121) gene transfer (P < 0.01). Entire endothelialization occurred at 30 days after VEGF gene transfer. In addition, higher expression of myocardial VEGF mRNA was still available.

CONCLUSIONSVEGF gene transfer by surgical suture can remarkably accelerate endothelialization of bioprosthesis, which may provide a new approach for inhibiting biological valve calcification and improve biocompatibility and long-term durability of the bioprosthesis.

Animals ; Bioprosthesis ; Endothelial Growth Factors ; analysis ; genetics ; Endothelium, Vascular ; physiology ; Female ; Gene Transfer Techniques ; Heart Valve Prosthesis ; Humans ; Lymphokines ; analysis ; genetics ; Male ; RNA, Messenger ; analysis ; Swine ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors

Until recently, vascular endothelial growth factor (VEGF) was the only growth factor proven to be specific and critical for blood vessel formation. Other long-known factors, such as the fibroblast growth factors (FGFs), platelet-derived growth factor, or transforming growth factor-beta, had profound effects in endothelial cells. But such factors were nonspecific, in that they could act on many other cells, and it seemed unlikely that these growth factors would be effective targets for treatment of endothelial cell diseases. A recently discovered endothelial cell specific growth factor, angiopoietin, has greatly contributed to our understanding of the development, physiology, and pathology of endothelial cells (Davis et al., 1996; Yancopoulos et al., 2000). The recent studies that identified and characterized the physiological and pathological roles of angiopoietin have allowed us to widen and deepen our knowledge about blood vessel formation and vascular endothelial function. Therefore, in this review, we describe the biomedical significance of these endothelial cell growth factors, the angiopoietins, in the vascular system under normal and pathological states.
Alternative Splicing ; Angiogenesis Factor/genetics/*metabolism ; Animal ; Cell Survival ; Endothelial Growth Factors/metabolism ; Endothelium, Vascular/cytology/*physiology ; Hematopoiesis/physiology ; Human ; Intercellular Signaling Peptides and Proteins/metabolism ; Lymphokines/metabolism ; Membrane Glycoproteins/genetics/*metabolism ; Neoplasm Proteins/metabolism ; Neovascularization, Pathologic ; Neovascularization, Physiologic ; Signal Transduction/physiology ; Urogenital System/physiology