Angiogenesis refers to the production of new blood vessels from the posterior veins of existing capillaries or capillaries, including degradation of the vascular basement membrane during activation, activation, proliferation and migration of vascular endothelial cells. Reconstruction of new blood vessels and vascular networks is a complex process involving multiple molecules of multiple cells. Angiogenesis is a complex process in which angiogenic factors and inhibitors are coordinated. Under normal conditions, the two are in equilibrium. Once this balance is broken, the vascular system is activated, causing excessive angiogenesis or inhibiting the destruction of the vascular system.
Angiogenesis is the growth of new capillary blood vessels that originate from existing capillaries and post-capillary venules. Tumor angiogenesis is an extremely complex process, which generally includes steps including vascular endothelial matrix degradation, endothelial cell migration, endothelial cell proliferation, endothelial cell tube branching to form a vascular ring, and formation of a new basement membrane. Due to the abnormal structure and function of the neovascularization of the tumor tissue, and the vascular matrix is imperfect, the microvascular is prone to leakage, so the tumor cells do not need to undergo a complicated invasion process and directly penetrate into the blood vessel to enter the bloodstream and are distant. The site forms a metastasis. More and more studies have shown that benign tumors have rare angiogenesis and slow blood vessel growth; most malignant tumors have dense angiogenesis and rapid growth. Therefore, angiogenesis plays an important role in the development and metastasis of tumors. The inhibition of this process will obviously prevent the development and spread of tumor tissues.
Examples of vasculogenesis proteins
Vasculogenesis proteins are small molecules of proteins originally isolated from human adenocarcinoma cultured cells. It can make new blood vessels grow in living tissue. Healthy non-cancerous tissues also produce this small molecule protein, with 35% of the sequences being homologous to the pancreatic ribonuclease.
Vascular endothelial growth factor (VEGF) is a highly specific pro-vascular endothelial growth factor that promotes increased vascular permeability, extracellular matrix degeneration, vascular endothelial cell migration, proliferation, and angiogenesis.
1. Promote endothelial cell proliferation VEGF is a specific mitogen of vascular endothelial cells, which promotes the growth of vascular endothelial cells in vitro and induces vascular proliferation in vivo. Especially in a hypoxic environment, VEGF binds to the VEGF receptor on the endothelial cell membrane, causing autophosphorylation of the receptor, thereby activating mitogen-activated protein kinase (MAPK), realizing the mitogenic properties of VEGF and inducing endothelial cell proliferation.
2. Promote vascular proliferation in hypoxic conditions, VEGF increases the activity of plasma zymogen activating factor by increasing the mRNA expression of plasma zymogen activating factor (PA) and plasma zymogen activating factor inhibitor-1 (PAI-1). It promotes extracellular protein hydrolysis and promotes the formation of new capillary blood vessels.
3. Increase vascular permeability VEGF is one of the strongest substances that increase vascular permeability and is achieved by small cell vesicles. It is characterized by rapid action and short duration.
4. Altering extracellular matrix In hypoxic environment, VEGF can induce plasma plasminogen activator and plasma lysogen activator inhibitor-1, as well as matrix collagenase, induced tissue factor and other expression in endothelial cells, and stimulate The V3 factor is released from endothelial cells, which alters the extracellular matrix, making it easier for blood vessels to grow.
Fibroblast growth factor (FGF) is a class of cellular signal transduction proteins involved in a variety of processes, most notably as a key element of normal development. Any irregularity in their function can lead to a series of developmental defects. These growth factors are commonly used as systems or local circulating molecules that activate the extracellular origin of cell surface receptors. The main feature of FGFs is that they bind to heparin and heparan sulfate, and it is therefore found that some of them are sequestered in the extracellular matrix of tissues containing heparan sulfate proteoglycans and are locally released upon injury or tissue remodeling.
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2. Wang JH.; et al. Mechanoregulation of gene expression in fibroblasts. Gene. 2007,391 (1–2): 1–15.