Vascular Endothelial Growth Factor Angiogenesis Research Articles

Evidence for the existence of a novel pregnancy-associated soluble variant of the vascular endothelial growth factor receptor, Flt-1.

Angiogenesis is essential in physiological processes including ovulation, implantation and pregnancy. One of the most potent regulators is the cytokine vascular endothelial growth factor (VEGF). We provide evidence for a novel pregnancy-associated soluble variant of the VEGF receptor Flt-1. VEGF ranged from undetectable to 157.3 pg/ml (mean 49.9 pg/ml, SD 48.4 pg/ml) in plasma samples from normal volunteers (n = 10), but was undetectable in plasma from pregnant women (n = 12) and amniotic fluid (n = 10). Recoveries of spiked VEGF were poor in pregnancy-related samples, indicating the presence of VEGF-binding activity which was confirmed using biosensor and chromatographic techniques. Partial purification and protein sequencing indicated a novel soluble form of Flt-1 with a subunit size of 150 kDa. Normally present as a multimeric structure of approximately 400-550 kDa, complexes of 600-700 kDa were formed following binding of multiple VEGF molecules. Reverse transcriptase polymerase chain reaction of Flt-1 in placenta, amnion, chorion, human umbilical vein endothelial cells and cord blood samples produced bands of the predicted sizes but failed to identify any additional RNA species, and possible reasons for this are discussed. Soluble Flt-1 may be important in regulating the actions of VEGF in angiogenesis and trophoblast invasion and may have therapeutic implications in diseases with inappropriate angiogenesis such as proliferative retinopathies and cancer.

Expression and response to hypoxia of vascular endothelial growth factor (VEGF) in rat and rabbit tissues.

VEGF is a potent and specific endothelial cell mitogen and an important regulator and inducer of angiogenesis. Recent finding of capillary budding in hypoxic rat brain suggested that hypoxia might initiate angiogenesis in brain. As a key factor of angiogenesis VEGF is thought to be potent in the basement membrane destruction and leakage. It can enhance microvascular permeability with a potency some 50,000 times that of histamine,11 which is likely to elicit hypoxic cerebral edema. The pathologic findings of cerebral thrombosis and petechial hemorrhages12 in high altitude cerebral edema are also consistent with VEGF physiological effects such as induction of thromboplastin activity5 and stimulation of von Willebrand factor release from endothelial cells.2 We surmise that VEGF may contribute to hihgh altitude cerebral edema (HACE). Here we report the expression and responce to hypoxia of VEGF mRNA, VEGF protein and its receptor (flt-1) in hypoxic tissues

Nachweis des angiogenen Zytokins Vascular Endothelial Growth Factor (VEGF) durch nicht radioaktive In-situ-Hybridisierung

In tumor angiogenesis Vascular Endothelial Growth Factor (VEGF) has an important role due to its target cell specificity. It is expressed by the tumor and effects on a paracrine pathway. To increase the understanding of its regulation, it is necessary to identify those cells releasing VEGF. This can be done by in situ hybridization (ISH). In this paper we present a protocol for non-radioactive ISH for VEGF colonic tissue. With this protocol it is possible to perform hybridization within one day.

The role of vascular endothelial growth factor in a murine chronic granulomatous tissue air pouch model of angiogenesis.

Chronic granulomatous inflammation may be considered an angiogenic-dependent process. Recently it has been demonstrated that vascular endothelial growth factor (VEGF) or vascular permeability factor is essential for tumour angiogenesis. Its role in inflammation-mediated angiogenesis has yet to be determined. In this study, the murine chronic granulomatous air pouch model was used to investigate the role of VEGF in angiogenesis. Animals were treated twice weekly with 10 micrograms per animal of neutralizing antibody to rh VEGF and the vascularity and granuloma dry weight were assessed after 7 days. This resulted in significant suppression of both angiogenesis and granuloma dry weight. Western blot analysis demonstrated the presence of VEGF; the levels of protein paralleled the angiogenic response. These results demonstrate for the first time that VEGF may be an important regulator of angiogenesis in inflammation.