Disease relevance of VEGF

• Plasmid-mediated VEGF gene transfer induces cardiomyogenesis and reduces myocardial infarct size in sheep [1].
• We conclude that plasmid-mediated VEGF gene transfer reduces myocardial infarct size by a combination of effects including neovascular proliferation, modification of fibrosis and cardiomyocyte regeneration [1].
• Notably, ORFV 006/132, 103, 109, 110, and 116 genes (VEGF, homologues of vaccinia virus A26L, A33R, and A34R, and a novel PPV ORF) show an unusual degree of intraspecies variability [2].
• The relationship between transplacental O2 diffusion and placental expression of PlGF, VEGF and their receptors in a placental insufficiency model of fetal growth restriction [3].
• In many cells, hypoxia stimulates VEGF expression [4].

Psychiatry related information on VEGF

• Color kinesis echography showed important improvements of regional fractional area change in the cell group (from 13.6% +/- 0.8% to 21.1% +/- 1.5%) and in the cell plus vascular endothelial growth factor group (from 12.8% +/- 0.9% to 18.7% +/- 2.3%) [5].

High impact information on VEGF

• ORFV2-VEGF showed mitogenic activity on bovine aortic and human microvascular endothelial cells and induced vascular permeability [6].
• These results indicate that VEGF-E is a novel type of endothelial growth factor, utilizing only one of the VEGF receptors, and carrying a potent mitogenic activity without affinity to heparin [7].
• Recently, a gene encoding a polypeptide with about 25% amino acid identity to mammalian VEGF was identified in the genome of Orf virus (OV), a parapoxvirus that affects sheep and goats and occasionally, humans, to generate lesions with angiogenesis [7].
• Resting myocardial perfusion (99mTc-sestamibi SPECT) was higher in VEGF-treated group than in empty plasmid group 15 days after myocardial infarction [1].
• After 15 days infarct area was 11.3+/-1.3% of the left ventricle in the VEGF group and 18.2+/-2.1% in the empty plasmid group (P<0.02) [1].

Chemical compound and disease context of VEGF

• The results demonstrate that hypoxia and dexamethasone are regulators of VEGF expression in ovine pulmonary artery smooth muscle cells [4].
• For study of VEGF inhibition, 13 premature newborn baboons (68% gestation) were treated with inhibitors of both prostaglandin and nitric oxide production to constrict the ductus and induce ductus wall hypoxia [8].
• By 6 days after birth, surrogate markers of hypoxia (HIF1alpha/VEGF mRNA) and cell death [dUTP nick-end labeling (TUNEL)-staining] increased, while glucose and ATP concentrations (bioluminescence imaging) decreased in the immature ductus [9].
• CONCLUSIONS: Heparin administration during LV hypertension increases heparin-binding angiogenic factors FGF-2 and VEGF in the LV and ameliorates decreases in LV perfusion capacity and capillary density [10].

Biological context of VEGF

• As angiogenesis and vasodilatation of the uterine and placental vascular beds are important at all stages of pregnancy, it is important to understand how VEGF and NO change throughout gestation in circulation [11].
• To examine the role of vascular endothelial growth factor (VEGF) in mediating angiogenesis and vascular permeability during fetal development, we determined the gene expression of VEGF in ovine fetal tissues [12].
• Ovine vascular endothelial growth factor: nucleotide sequence and expression in fetal tissues [12].
• As the mitogen-activated protein kinase (MAPK) signal cascade has been widely associated with cell growth in response to growth factors, herein we investigate whether bFGF, EGF, and VEGF also stimulate expression of endothelial nitric oxide synthase (eNOS) via activation of the MAPK cascade in ovine fetoplacental artery endothelial cells [13].
• Associated with the periovulatory period was intense expression of VEGF by thecal cells at the basement membrane and subsequent invasion of the granulosa layers by these VEGF-positive cells immediately after ovulation [14].

Anatomical context of VEGF

• Vascular endothelial growth factor (VEGF) has been reported to increase eNOS expression and NO production in endothelial cell cultures [11].
• The pattern of the rise in NOx in circulating plasma was not directly associated with changes in VEGF regardless of the number of fetuses present [11].
• However, circulating concentrations of NOx and VEGF appear to, respectively, follow patterns of uterine blood flow and angiogenesis of the uterus [11].
• CLINICAL RELEVANCE: Exogenous VEGF application for ACL reconstruction can induce an increase in knee laxity and a decrease in the stiffness of the grafted tendon at least temporarily after ACL reconstruction [15].
• VEGF protein was localized in epithelial cells of the placenta and fetal kidney, and in hepatocytes of the fetal liver [12].

Associations of VEGF with chemical compounds

• We have previously shown that angiogenic factors from corpora lutea are primarily heparin binding and that one of these factors is similar to vascular endothelial growth factor (VEGF) [16].
• Similarly, P-UAEC make PGI2 in response to AII, ATP, bFGF, and VEGF, whereas NP-UAEC make PGI2 only in response to ATP and VEGF [17].
• Thus, P-UAEC make NO in response to AII, ATP, bFGF, EGF, and VEGF, whereas NP-UAEC make NO in response to bFGF, EGF, and VEGF only [17].
• Therefore, our results indicate that cyclic stretch upregulates VEGF expression via the TGF-beta1-dependent activation of NAD(P)H oxidase and increased generation of ROS [18].
• Also, in some cases, dexamethasone blocks VEGF expression [4].

Other interactions of VEGF

• This was accompanied by changes in placental VEGF and IGFBP expression [19].
• Maximum expression was found at 24 h and 15% stretch (VEGF: 1.8-fold; FGF-2: 1.9-fold) [20].
• The VEGF receptors FLT-1 and KDR could be detected on endothelial cells of blood vessels [21].
• To determine whether lung VEGF expression is decreased in an experimental model of persistent pulmonary hypertension of the newborn (PPHN), we measured lung VEGF and VEGF receptor protein content from fetal lambs 7-10 days after ductus arteriosus ligation (132-140 days gestation; term = 147 days) [22].
• Double immunocytochemistry with VEGF and prolactin or luteinising hormone-beta (LH-beta) antibodies demonstrated that the VEGF-secreting cells are not lactotrophs or gonadotrophs [23].

Analytical, diagnostic and therapeutic context of VEGF

• In addition, an N-terminal peptide was synthesized from the translated ovine cDNA sequence for VEGF and an antiserum was raised against this peptide for use in western immunoblotting procedures [16].
• Cloning and sequence analysis of the most abundant form of ovine VEGF cDNA in the placenta confirmed the prediction of a 164-amino acid peptide, with a putative N-terminal signal sequence of 26 amino acids [12].
• Expression of VEGF and FGF-2 was determined by Northern blot analysis [20].
• Little is known about the growth factors involved in lung injury and repair, but vascular endothelial growth factor (VEGF) has recently been reported in several animal models of lung injury [4].
• A significantly lower atrophy score was observed in the groups treated with bFGF (1.4 +/- 0.18, p < 0.05), RGTA (1.59 +/- 0.17, p < 0.05), and VEGF (1.96 +/- 0.14, NS), as compared with the control group (2.48 +/- 0.16) [24].

References