Vascular Endothelial Growth Factor Signaling Pathways: Therapeutic Perspective

Abstract

The establishment of a vascular supply is one of the earliest and most important events occurring during embryonic development. Growth and maturation of a functional vascular network are complex and still incompletely understood processes involving orchestrated activation of vascular progenitors in the early stages of embryonic development followed by vasculogenesis and angiogenesis. These processes require a tightly regulated activation of several growth factors and their receptors. The role of vascular endothelial growth factors (VEGF) and their receptors has been studied extensively due to their prominent role during blood vessel formation. Mice deficient in various VEGF ligands or receptors show serious defects in vascular formation and maturation. Moreover, members of the VEGF family are involved in other significant biological processes, including lymphangiogenesis, vascular permeability, and hematopoiesis. Importantly, VEGF is released by tumor cells and induces tumor neovascularization. It is now well established that the VEGF axis represents an important target for antitumor therapy. Aberrant VEGF signaling is also a feature of several other pathologic conditions, such as age-related macular degeneration and rheumatoid arthritis.

Vascular Endothelial Growth Factor (VEGF) Receptor-2 Tyrosine 1175 Signaling Controls VEGF-induced von Willebrand Factor Release from Endothelial Cells via Phospholipase C-γ1- and Protein Kinase A-dependent Pathways

“…2 is a crucial regulator of vasculogenesis, angiogenesis, and vascular permeability (1)(2)(3)(4)(5). A number of studies have suggested that VEGF promotes proliferation, migration, and survival of endothelial cells (1,4).…”

“…A number of studies have suggested that VEGF promotes proliferation, migration, and survival of endothelial cells (1,4). VEGF (also termed VEGF-A) is a member of the growth factor subfamily that includes VEGF-B, -C, -D, and -E and placental growth factor (PlGF).…”

“…Identification (4,34), have been linked to the activation of PLC␥1 (23, 34 -36). Therefore, we investigated the roles of these residues in PLC␥1 activation and vWF release by point mutagenesis.…”

The Importance of Cellular VEGF Bioactivity in the Development of Glomerular Disease

“…VEGF-A promotes angiogenesis, and belongs to the VEGF family of proteins, which also includes VEGF-B, VEGF-C, VEGF-D and placental-derived growth factor [2]. There are many isoforms of VEGF-A that are named according to their number of amino acids, i.e.…”

Quercetin Inhibits Vascular Endothelial Growth Factor-Induced Choroidal and Retinal Angiogenesis in vitro

“…VEGF is a potent proangiogenic factor that stimulates endothelial cell proliferation, migration and tube formation - key processes of angiogenesis [23]. The biologically relevant VEGF signaling events are mainly mediated by VEGFR-2 [24,25,26]. Activation of VEGFR-2 contributes to the phosphorylation of multiple downstream signals including ERK, JNK, PI3K, AKT, P70S6K and p38MAPK that subsequently promote the proliferation migration and tube formation of endothelial cells [24].…”