Angiostatin is a natural peptide that inhibits angiogenesis and inhibits angiogenesis by preventing the proliferation and migration of vascular endothelial cells.
Background of Angiostatin
The Angiostatin was first discovered in 1994 by M.J. O'Reilly, M.S. Boehm, and others from the Harvard Cancer Society (CCR) in the United States. It is a natural peptide, which is expressed and secreted by cloned Escherichia coli. The fragment between 161 and 352 of 196 amino acid residues is its active site. The main function of Angiostatin is to inhibit the growth of tumor blood vessels, which can slow down and prevent tumor growth and metastasis. In addition, the Angiostatin protein has been found to have various biological effects such as anti-inflammatory, antiviral, and antidepressant effects.
Function of Angiostatin
Research has found that the Angiostatin inhibits tumor angiogenesis through various mechanisms. Firstly, the Angiostatin can directly act on receptors on the surface of endothelial cells, thereby preventing their proliferation and differentiation, and thereby inhibiting vascular growth. Secondly, Angiostatin can stimulate the expression of thrombospondin, which is a strong inhibitor of angiogenesis. In addition, Angiostatin protein can also inhibit the basal metastasis and migration of vascular endothelial cells, thereby reducing tumor invasion and metastasis.
Angiostatin related Signal pathway
The mechanism of Angiostatin inhibiting tumor angiogenesis is complex, and its signal pathways mainly include two types: vascular endothelial cell (EC) signal transduction and vascular smooth muscle cell (VSMC) signal transduction.
Signal transduction in vascular endothelial cells: The Angiostatin mainly exerts anti-angiogenic effects by inhibiting the VEGF and FGF-2 signaling pathways. VEGF mediates signals through two receptors, VEGFR-2 and VEGFR-1, thereby promoting the proliferation and migration of vascular endothelial cells. FGF-2 also enables angiogenesis, and its role is played through FGFR-1 and FGFR-2 mediated signal pathways. Angiostatin can directly bind to VEGFR-2, VEGFR-1, and FGFR-1, and block the signals they mediate, thereby inhibiting angiogenesis.
Vascular smooth muscle cell signal transduction: In addition to endothelial cell signal transduction, Angiostatin protein can also indirectly act on the signal transduction pathway of vascular smooth muscle cells, thereby inhibiting the formation of new blood vessels. Angiostatin protein can stimulate platelet aggregation in blood vessels, thereby inducing the release of platelet derived growth factor (PDGF) and collagenase (MMP) from platelets. The presence of these two molecules can indirectly reduce the ability of angiogenesis.
Angiostatin related diseases and its effects
The Angiostatin is associated with many diseases, especially the angiogenesis and metastasis processes related to tumors.
1. Tumor: At first, researchers found that Angiostatin can inhibit the growth of human breast cancer and mouse melanoma. Subsequent studies have shown that the Angiostatin also has inhibitory effects on the growth and metastasis of many other tumor types. For example, it can inhibit the growth and metastasis of lung cancer, breast cancer, prostate cancer and other tumors.
2. Coronary heart disease: Another function of Angiostatin is to inhibit the formation of coronary heart disease, mainly by inhibiting the occurrence of angiogenesis and atherosclerosis, and reducing the incidence of cardiovascular events.
3. Premature birth: Angiostatin is an anti-inflammatory molecule that often increases demand during pregnancy. Previous studies have shown that Angiostatin not only protects against risk factors for premature birth, but also increases the birth rate of early fetuses.
Medical applications of Angiostatin
The application of Angiostatin in medicine is mainly to inhibit angiogenesis to achieve the purpose of anti-tumor and treatment of cardiovascular diseases. Currently, many studies are utilizing Angiostatin to develop new drugs for tumors and coronary heart disease. In addition, Angiostatin can also be used to prepare various biosensors and biochips for detecting new blood vessels in the blood circulation system.
List of Angiostatin related drugs under research
At present, some Angiostatin related drugs have entered the clinical trial stage. Here are some representative research drugs:
Endostatin: In 1998, Jude Nickerson of MIT Camden Laboratory successfully fused the C-terminal sequence of Angiostatin with the external region of human fibroblast growth factor receptor 1 to obtain a new drug Endostatin. Endostatin is an anti-tumor biological drug and is considered one of the most promising drugs based on the Angiostatin.
2-Methoxyestradiol (2-ME): 2-Methoxyestradiol is a special estrogen metabolite with strong anti-tumor and anti-angiogenic activity. Researchers have found that 2-Methodestradiol can simulate the action of Angiostatin, thereby inhibiting angiogenesis and tumor growth.
Canstatin: Canstatin is a derivative of Angiostatin, which contains the C-terminal sequence of Angiostatin and has the ability to inhibit tumor and angiogenesis. It is widely used in the treatment of tumors and other angiogenic related diseases.
