Vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF), is a highly specific vascular endothelial cell growth factor that promotes increased vascular permeability and extracellular stromal degeneration, vascular endothelial cell migration, proliferation, and angiogenesis.
Vascular endothelial growth factor is a family including VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E, and placental growth factor (PGF). Usually VEGF is VEGF-A. VEGF-A can promote neovascularization and increase vascular permeability. VEGF-B plays a role in non-angiogenic tumors. VEGF-C and VEGF-D play a role in the formation of neovascular and lymphatic vessels in cancer tissues. VEGF-E is also a potential neovascularization factor. PGF promotes neovascularization, increases vascular permeability, and significantly increases the expression of PGF in experimental choroidal neovascularization.
Vascular endothelial growth factor AN (VEGF-A) is a protein encoded by the VEGF gene in humans. VEGF-A mainly interacts with VEGFR1 and -R2 receptors that are prominently present on the endothelial cell membrane, and shows significant activity on vascular endothelial cells. Although it does affect many other cell types. In vitro, VEGF-A has been shown to stimulate endothelial cell mitosis and cell migration. VEGF-A is also a vasodilator that increases microvascular permeability and was originally called a vascular permeability factor.
Figure 1. VEGF-A.
Vascular endothelial growth factor B, also known as VEGF-B, is a protein encoded by the VEGF-B gene in humans. VEGF-B is a growth factor that belongs to the vascular endothelial growth factor family, of which VEGF-A is the most famous member. VEGF-B's role in the vasculature is less pronounced: Although VEGF-A is important for angiogenesis, such as during development or under pathological conditions, VEGF-B seems to play a pathological role in maintaining neovascularization Under blood vessels.
Figure 2. VEGF-B.
Vascular endothelial growth factor C (VEGF-C) is a member of the platelet-derived growth factor / vascular endothelial growth factor (PDGF/VEGF) family. The main function of VEGF-C is in lymphangiogenesis, which promotes survival mainly through its receptor VEGFR-3. It was discovered in 1996 as a ligand for orphan receptor VEGFR-3. In addition to its effects on the lymphatic vessels, it can also promote the growth of blood vessels and regulate their permeability.
Figure 3. VEGF-C.
High-affinity receptors that specifically bind to vascular endothelial growth factor are called vascular endothelial growth factor receptors (vascular endothelial growth factor receptors, VEGFRs), and are mainly divided into three types of VEGFR-1, VEGFR-2, and VEGFR-3. VEGFR-1 and VEGFR-2 are mainly distributed on the surface of tumor vascular endothelial cells and regulate tumor angiogenesis; VEGFR-3 is mainly distributed on the surface of lymphatic endothelium and regulate tumor angiogenesis.
1. Promoting endothelial cell proliferation VEGF is a specific mitogen of vascular endothelial cells, which can promote the growth of vascular endothelial cells in vitro and induce vascular proliferation in vivo. Especially in the hypoxic environment, VEGF binds to the VEGF receptor on the endothelial cell membrane, causing the phosphorylation of the receptor, thereby activating mitogen-activated protein kinase (MAPK), realizing the mitogen characteristics of VEGF, and inducing endothelial cell proliferation.
2. Promote angiogenesis in a hypoxic environment, VEGF can increase the activity of plasma zymogen activator by increasing the mRNA expression of plasma zymogen activator (PA) and plasma zymogen activator inhibitor-1 (PAI-1). Promote extracellular proteolysis, and then promote the formation of new capillaries.
3. Increasing vascular permeability VEGF is one of the strongest substances that can increase vascular permeability, which is achieved through small vesicles of cells. It is characterized by rapid action and short duration.
4. Change the extracellular matrix. In the hypoxic environment, VEGF can induce the expression of plasma prolysin activator and plasma lysogen activator inhibitor-1, as well as the expression of matrix collagenase and tissue factor in endothelial cells. Factor V3 is released from endothelial cells, thereby altering the extracellular matrix and making it easier for blood vessels to grow.