Vascular endothelial growth factor mRNA expression and arteriovenous balance in response to prolonged, submaximal exercise in humans

2003 ◽  
Vol 285 (4) ◽  
pp. H1759-H1763 ◽  
Author(s):  
N. Hiscock ◽  
C. P. Fischer ◽  
H. Pilegaard ◽  
B. K. Pedersen
Keyword(s):  
Skeletal Muscle ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Submaximal Exercise ◽  
Vascular Endothelial ◽  
Vegf Mrna ◽  
Protein Balance ◽  
Mrna Content ◽  
Endothelial Growth Factor ◽  
Vegf Protein

Angiogenesis, the growth of new blood vessels from existing ones, occurs in the skeletal muscle as an adaptive response to exercise that satisfies the increased requirement of this tissue for oxygen delivery and metabolic processes. Of the factors that have been identified to regulate this process, the endothelial cell mitogen vascular endothelial growth factor (VEGF) has been proposed to play a key role. The aim of this study was to measure the skeletal muscle VEGF mRNA content and arteriovenous protein balance across the working leg in response to a single bout of prolonged, submaximal exercise. Seven physically active males completed 3 h of two-legged kicking ergometry. Muscle biopsies were collected from the vastus lateralis muscle from both working legs, and blood samples were collected from one femoral artery and femoral vein before, during, and in recovery from exercise. We show that the exercise stimulus elicited a decrease in VEGF protein arteriovenous balance across the exercising leg ( P = 0.007), and a ninefold elevation in skeletal muscle VEGF mRNA expression ( P < 0.001). The changes in VEGF protein balance and mRNA content were most pronounced 1 h after the cessation of exercise. In conclusion, these findings demonstrate that submaximal exercise, suitable for humans with low CV fitness, induces a decrease in VEGF arteriovenous balance that is likely to be of clinical significance in promoting angiogenic effects.

scholarly journals Basic Fibroblast Growth Factor-Mediated Overexpression of Vascular Endothelial Growth Factor in 1F6 Human Melanoma Cells is Regulated by Activation of PI-3K and p38 MAPK

2009 ◽  
Vol 31 (3) ◽  
pp. 179-190
Author(s):  
Dennis Fontijn ◽  
Linda J. W. Bosch ◽  
Monique C. A. Duyndam ◽  
Maria P. A. van Berkel ◽  
Maarten L. Janmaat ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Protein Secretion ◽  
Human Melanoma ◽  
Vascular Endothelial ◽  
Fibroblast Growth ◽  
Vegf Mrna ◽  
Endothelial Growth Factor ◽  
Vegf Protein

Background: 1F6 human melanoma xenografts overexpressing either the 18 kD (18kD) form or all (ALL) forms of human basic fibroblast growth factor (bFGF) demonstrate an abundant number of microvessels and accelerated growth. We now examined whether bFGF mediates vascular endothelial growth factor (VEGF) expression.Methods: Quantitative RT-PCR was used to determine bFGF and VEGF mRNA, VEGF protein secretion was measured by ELISA and VEGF promoter activation was assessed by a dual luciferase activity assay. Western blot was carried out to detect phosphorylation of bFGF-regulated target proteins.Results: In 1F6-18kD and 1F6-ALL clones VEGF mRNA was increased 4- to 5-fold and VEGF protein secretion was highly stimulated due to activation of the VEGF promotor. PI-3K, p38 MAPK and ERK1/2 MAPK pathways were activated, while inhibition of PI-3K or p38 resulted in, respectively, 55% and up to 70% reduction of VEGF mRNA overexpression. A concurrent 60% decrease in VEGF protein secretion was mostly apparent upon inhibition of PI-3K. Inhibition of ERK1/2 hardly affected VEGF mRNA or protein secretion. Two unselected human melanoma cell lines with high metastatic potential contained high bFGF and VEGF, while three non- or sporadically metastatic cell lines displayed low bFGF and VEGF.Conclusion: These data indicate that stimulation of VEGF protein secretion in response to bFGF overexpression may contribute to increased vascularization and enhanced aggressiveness in melanoma.

Expression of Vascular Endothelial Growth Factor in Human Umbilical Vein Endothelial Cells Stimulated with Interleukin-1α

2000 ◽  
Vol 83 (06) ◽  
pp. 949-955 ◽  
Author(s):  
Hiroyuki Itaya ◽  
Satoki Nasu ◽  
Hidemi Yoshida ◽  
Yuki Matsubara ◽  
Koji Fujimoto ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Umbilical Vein ◽  
Vascular Endothelial ◽  
Vegf Mrna ◽  
Interleukin 1Α ◽  
Umbilical Vein Endothelial Cells ◽  
Endothelial Growth Factor ◽  
Vegf Protein

SummaryVascular endothelial growth factor (VEGF) is a specific mitogen for endothelial cells. We studied the production of VEGF by human umbilical vein endothelial cells (HUVEC) and smooth muscle cells (SMC) in response to the stimulation with interleukin-1α (IL-1α). HUVEC expressed VEGF mRNA in response to IL-1α in doseand time-dependent manners. In HUVEC VEGF protein was detected only in cell lysates whereas in SMC most of the VEGF protein was detected in the conditioned medium. Immunofluorescent staining also confirmed the cell-associated VEGF in HUVEC. IL-1α also induced the expression of mRNA for IL-1α itself in HUVEC. Cycloheximide treatment of HUVEC slightly inhibited the IL-1α-induced expression of VEGF mRNA, and IL-1α may mediate, at least in part, VEGF expression in response to IL-1α. The growth of HUVEC stimulated with IL-1α was inhibited by a neutralizing antibody against VEGF. We conclude that IL-1α and VEGF may play an important role in autocrine growth regulation of HUVEC.

Effects of Hypocrellin A on Expression of Vascular Endothelial Growth Factor and Endothelin-1 in Human Umbilical Endothelial Cells

2007 ◽  
Vol 35 (04) ◽  
pp. 713-723 ◽  
Author(s):  
Lei Dang ◽  
J. Paul Seale ◽  
Xianqin Qu
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Endothelial Dysfunction ◽  
Protein Expression ◽  
Vascular Endothelial ◽  
Naturally Occurring ◽  
Hypocrellin A ◽  
Endothelial Growth Factor ◽  
Vegf Protein

Increased endothelin-1 (ET-1), vascular endothelial growth factor (VEGF) and activation of protein kinase C (PKC) are co-contributors to endothelial hyperpermeability in diabetes. Several lines of evidence have suggested a hypothesis that activation of specific PKC isoforms are the causative factor in ET-1 and VEGF mediated endothelial dysfunction. In the present study, we tested this hypothesis with hypocrellin A, a naturally occurring PKC inhibitor from a Chinese plant. Human umbilical vein endothelial cells (HUVECs) were incubated with 20 mM glucose in both the presence and absence of hypocrellin A, after which, the protein expression and release of VEGF and mRNA expression and release of ET-1 were measured. VEGF and ET-1 were released into the medium and expressions of VEGF protein and ET-1 mRNA were significantly increased in HUVECs incubated with 20 mM glucose. Hypocrellin A (150 nM) significantly decreased VEGF release (117 ± 3 vs. 180 ± 11 pg/mg, p < 0.05) and VEGF protein expression (from 130 ± 14% to 88 ± 18.5%, p < 0.05). ET-1 release was also reduced in hypocrellin A treated HUVECs (63.3 ± 9.9 vs. 75.2 ± 12.6 ng/mg). Hypocrellin A significantly reversed the effect of high glucose on ET-1 mRNA expression ( p < 0.05). The results revealed that PKC activation plays a pivotal role in VEGF and ET-1 mediated endothelial permeability. The naturally occurring compound hypocrellin A may be a potentially novel treatment for endothelial dysfunction in diabetes.

scholarly journals The vascular endothelial growth factor (VEGF) isoforms: differential deposition into the subepithelial extracellular matrix and bioactivity of extracellular matrix-bound VEGF.

1993 ◽  
Vol 4 (12) ◽  
pp. 1317-1326 ◽  
Author(s):  
J E Park ◽  
G A Keller ◽  
N Ferrara
Keyword(s):  
Extracellular Matrix ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Vascular Endothelial ◽  
Vegf Mrna ◽  
Angiogenic Potential ◽  
Molecular Masses ◽  
Matrix Bound ◽  
Endothelial Growth Factor ◽  
Vegf Isoforms

Vascular endothelial growth factor (VEGF)mRNA undergoes alternative splicing events that generate four different homodimeric isoforms, VEGF121, VEGF165, VEGF189, or VEGF206. VEGF121 is a nonheparin-binding acidic protein, which is freely diffusible. The longer forms, VEGF189 or VEGF206, are highly basic proteins tightly bound to extracellular heparin-containing proteoglycans. VEGF165 has intermediate properties. To determine the localization of VEGF isoforms, transfected human embryonic kidney CEN4 cells expressing VEGF165, VEGF189, or VEGF206 were stained by immunofluorescence with a specific monoclonal antibody. The staining was found in patches and streaks suggestive of extracellular matrix (ECM). VEGF165 was observed largely in Golgi apparatus-like structures. Immunogold labeling of cells expressing VEGF189 or VEGF206 revealed that the staining was localized to the subepithelial ECM. VEGF associated with the ECM was bioactive, because endothelial cells cultured on ECM derived from cells expressing VEGF189 or VEGF206 were markedly stimulated to proliferate. In addition, ECM-bound VEGF can be released into a soluble and bioactive form by heparin or plasmin. ECM-bound VEGF189 and VEGF206 have molecular masses consistent with the intact polypeptides. The ECM may represent an important source of VEGF and angiogenic potential.

scholarly journals Myocyte vascular endothelial growth factor is required for exercise-induced skeletal muscle angiogenesis

2010 ◽  
Vol 299 (4) ◽  
pp. R1059-R1067 ◽  
Author(s):  
I. Mark Olfert ◽  
Richard A. Howlett ◽  
Peter D. Wagner ◽  
Ellen C. Breen
Keyword(s):  
Skeletal Muscle ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Exercise Training ◽  
Metabolic Adaptation ◽  
Vascular Endothelial ◽  
Vegf Expression ◽  
Running Speed ◽  
Endothelial Growth Factor ◽  
Adaptation To Exercise

We have previously shown, using a Cre-LoxP strategy, that vascular endothelial growth factor (VEGF) is required for the development and maintenance of skeletal muscle capillarity in sedentary adult mice. To determine whether VEGF expression is required for skeletal muscle capillary adaptation to exercise training, gastrocnemius muscle capillarity was measured in myocyte-specific VEGF gene-deleted (mVEGF−/−) and wild-type (WT) littermate mice following 6 wk of treadmill running (1 h/day, 5 days/wk) at the same running speed. The effect of training on metabolic enzyme activity levels and whole body running performance was also evaluated in mVEGF−/− and WT mice. Posttraining capillary density was significantly increased by 59% ( P < 0.05) in the deep muscle region of the gastrocnemius in WT mice but did not change in mVEGF−/− mice. Maximal running speed and time to exhaustion during submaximal running increased by 20 and 13% ( P < 0.05), respectively, in WT mice after training but were unchanged in mVEGF−/− mice. Training led to increases in skeletal muscle citrate synthase (CS) and phosphofructokinase (PFK) activities in both WT and mVEGF−/− mice ( P < 0.05), whereas β-hydroxyacyl-CoA dehydrogenase (β-HAD) activity was increased only in WT mice. These data demonstrate that skeletal muscle capillary adaptation to physical training does not occur in the absence of myocyte-expressed VEGF. However, skeletal muscle metabolic adaptation to exercise training takes place independent of myocyte VEGF expression.

scholarly journals Pitfalls in the Measurement of Circulating Vascular Endothelial Growth Factor

2001 ◽  
Vol 47 (4) ◽  
pp. 617-623 ◽  
Author(s):  
Wolfgang Jelkmann
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Neutralizing Antibodies ◽  
Inflammatory Diseases ◽  
Vascular Endothelial ◽  
Malignant Diseases ◽  
Vegf Mrna ◽  
Medline Search ◽  
Healthy Humans ◽  
Endothelial Growth Factor

Abstract Background: Vascular endothelial growth factor (VEGF) is a protein with antiapoptotic, mitogenic, and permeability-increasing activities specific for vascular endothelium. VEGF mRNA, which has five isoforms, is produced by nonmalignant cells in response to hypoxia and inflammation and by tumor cells in constitutively high concentrations. Because VEGF plays a crucial role in physiological and pathophysiological angiogenesis, measurements of circulating VEGF are of diagnostic and prognostic value, e.g., in cardiovascular failures, inflammatory diseases, and malignancies. However, there are major quantitative differences in the published results. This review attempts to identify reasons for these disparities. Approach: The literature was reviewed through a Medline search covering 1995 to 2000. A selection of exemplary references had to be made for this perspective overview. Content: Data are included from studies on healthy humans, gynecological patients, and persons suffering from inflammatory or malignant diseases. The results indicate that competitive immunoassays detect the total amount of circulating VEGF, which enables observations regarding the increase in VEGF in pregnancy and preeclampsia to be made. In these cases, capture immunoassays utilizing neutralizing antibodies are insufficient because of an accompanying increase in VEGF-binding soluble receptors (sFlt-1). Measurements of circulating free VEGF are useful for study of malignant diseases, which are associated with both genetically and hypoxia-induced overproduction of VEGF. The VEGF isoform specificity of the antibodies is also critical because both VEGF121 and VEGF165 are secreted. It is important to consider that platelets and leukocytes release VEGF during blood clotting. Conclusions: Future efforts should concentrate on the balance between free VEGF, total VEGF, and sFlt-1. Plasma, rather than serum, should be used for analysis.

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