Disease relevance of VEGFA

• Because myocardial and peripheral edema and systemic hypotension occur frequently after cardiac operations, we examined the effects of cardiopulmonary bypass (CPB) and cardioplegia on gene expressions of VEGF protein and the VEGF tyrosine kinase receptor flk-1 and coronary vascular responses to VEGF [1].
• Vascular endothelial growth factor (VEGF) is an endothelial-specific mitogen that is normally expressed only in low levels in normal arteries but may be involved in the progression of both vascular disease and cancer [2].
• Platelet-derived growth factor-B enhances glioma angiogenesis by stimulating vascular endothelial growth factor expression in tumor endothelia and by promoting pericyte recruitment [3].
• A factor other than hypoxia, perhaps the earlier appearance of another growth factor, transforming growth factor beta-1, may positively regulate VEGF appearance in the wound fluid [4].
• OBJECTIVES: We sought to optimize vascular endothelial growth factor (VEGF) treatment for therapeutic angiogenesis in myocardial ischemia, we explored the efficacy of five different regimens [5].

High impact information on VEGFA

• The inhibitory effect of ES on vascular endothelial growth factor-induced endothelial cell migration was blocked by the ES-binding SAS-domains and by heparin oligosaccharides (12mers) similar in length to the ES-binding SAS-domains, but not by 6mers capable of FGF binding [6].
• Vascular endothelial growth factor (VEGF) has two highly homologous tyrosine kinase receptors: Flt-1 (VEGFR-1) and KDR (VEGFR-2) [7].
• BACKGROUND: Vascular endothelial growth factor (VEGF) is a heparin-binding glycoprotein that plays a critical role in angiogenesis, vascular remodeling, and regulation of vascular tone and permeability [1].
• CONCLUSIONS: This study shows that VEGF protein and its flk-1 receptor gene expressions are selectively increased and the potent VEGF-induced vascular responses are enhanced in the coronary microcirculation after blood cardioplegia [1].
• Myocardial and skeletal muscle specimens were obtained for Northern analysis of VEGF protein, flk-1 receptor, and basic fibroblast growth factor (bFGF) mRNA before CPB and after 2 hours of reperfusion [1].

Chemical compound and disease context of VEGFA

• CONCLUSIONS: L-Arginine supplementation can restore normal endothelium-dependent vasorelaxation and angiogenic response to vascular endothelial growth factor in a swine model of chronic myocardial ischemia with hypercholesterolemia-induced endothelial dysfunction [8].
• Hypoxia increased VEGF as well as O2- production in swine granulosa cells without impairing cell growth; in addition, it decreased NO output [9].
• The time dependence of the dexamethasone effect correlated with a changed mechanism by which hypoxia induced VEGF expression [10].
• Because the barbiturates, methohexital (MH) and thiopental (TP), induced a dose-dependent reduction in hypoxia-induced permeability changes of BMEC, the effect of both barbiturates on the VEGF expression during hypoxia was investigated [11].
• Nitric oxide availability is decreased in patients with coronary disease, a possible explanation for the humble results of VEGF in clinical trials [12].

Biological context of VEGFA

• Nevertheless, when treatments were associated, a reduction of LPS-induced apoptosis was always observed; the reduction was maximal when all the treatments (HS + Hemin + VEGF) were associated [13].
• In conclusion, this study demonstrates that LPS is effective in evoking "the heat shock response" with an increase of nonspecific protective molecules (namely Hsp70 and Hsp32) and of VEGF, a specific EC growth factor [13].
• VEGF upregulation in the proliferative zone after ischemic damage may play a role in stimulating vascular invasion and granulation tissue formation in the necrotic hypertrophic zone of the epiphyseal cartilage [14].
• The objectives of the present study were to determine concentrations of VEGF in fetal blood and placental fluids as well as placental and adjacent endometrial mRNA expression of VEGF, VEGF-R1, and VEGF-R2 on Days 30, 50, 70, 90, and 110 of gestation in Yorkshire and Meishan pigs [15].
• VEGF, VEGFR-1 and VEGFR-2 immunoreactivity in the porcine arteries of vascular subovarian plexus (VSP) during the estrous cycle [16].

Anatomical context of VEGFA

• This study aimed at determining whether an LPS exposure is effective in inducing apoptosis in primary cultures of porcine aortic endothelial cells and in stimulating heat shock protein (Hsp)70 and Hsp32 production as well as vascular endothelial growth factor (VEGF) secretion [13].
• This study suggests that VEGF facilitates the repair of the necrotic epiphyseal cartilage, which is essential for restoration of endochondral ossification and re-establishment of the growth of the immature femoral head after ischemic necrosis [14].
• Differential expression of the vascular endothelial growth factor-receptor system in the gravid uterus of yorkshire and Meishan pigs [15].
• Day 90 Meishan conceptuses exhibited marked increases (P < 0.05) in placental VEGF mRNA expression as well as fetal blood and allantoic fluid concentrations of VEGF, which remained elevated through Day 110 [15].
• Our study revealed the presence of VEGF and its receptors in endothelial and smooth muscle cells of VSP arteries [16].

Associations of VEGFA with chemical compounds

• Heat shock protein 70, heat shock protein 32, and vascular endothelial growth factor production and their effects on lipopolysaccharide-induced apoptosis in porcine aortic endothelial cells [13].
• The porcine VEGF is shorter by one amino acid as compared to human VEGF, but a potential glycosylation site is present at Asn-74 [17].
• Nicotine and cotinine up-regulate vascular endothelial growth factor expression in endothelial cells [2].
• We show here, using an intact porcine common carotid artery perfusion culture model, that nicotine and cotinine, the major product of nicotine metabolism, cause a significant increase in endothelial cell VEGF expression [2].
• VEGF-induced activation of phosphoinositide 3-kinase is dependent on focal adhesion kinase [18].

Regulatory relationships of VEGFA

• Moreover, vascular endothelial growth factor was more abundantly expressed and Akt was more strongly activated in the ischemic region of the G-CSF treatment group than of control group [19].

Other interactions of VEGFA

• RESULTS: Vascular endothelial growth factor and MCP-1 concentrations increased in a time-related manner [20].
• Vascular endothelial growth factor treatment was ineffective in the CHOL group (circumflex/left anterior descending coronary artery blood flow ratios: 0.95 [rest] and 0.74 [pace] before-after treatment; P < .05 compared with the NORM group) [8].
• HIF-1 was transcriptionally active in LLC-PK(1) cells, as demonstrated by luciferase reporter gene assays using the vascular endothelial growth factor promoter or a synthetic promoter construct containing three hypoxia-inducible elements [21].
• In the operated ureter elevated expression of keratinocyte growth factor, vascular endothelial growth factor, TGF-alpha, TGF-beta 1, TGF-beta 3 and integrin was detected 2 hours after the operation and sustained for 7 to 14 days after the procedure [22].
• Gene expression in a swine model of right ventricular hypertrophy: intercellular adhesion molecule, vascular endothelial growth factor and plasminogen activators are upregulated during pressure overload [23].

Analytical, diagnostic and therapeutic context of VEGFA

• RESULTS: Western blot analysis and RPA showed increased VEGF protein and mRNA expression, respectively, in the epiphyseal cartilage of the infarcted heads compared with the contralateral normal heads [14].
• PCR detection, and verification of the identity of the PCR products by Southern hybridization, confirmed wide expression of VEGF in different porcine tissues [17].
• Northern blot analysis with a radiolabeled porcine specific VEGF probe, showed one major (3.9 kb) and one minor (1.7 kb) mRNA species expressed in all four chambers of the heart [17].
• Myocardial VEGF expression after cardiopulmonary bypass and cardioplegia [1].
• VEGF mRNA levels were compared between groups using reverse transcriptase-polymerase chain reaction, whereas protein level changes were demonstrated with Western blotting and immunohistochemistry [2].

References