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The secret language of blood vessels: Why is signaling by angiopoietins so important for inflammation and cancer?
In vascular biology, angiopoietins are known as a series of angiogenic factors that go hand in hand and play a pivotal role in embryonic and postnatal angiogenesis. Signaling by angiopoietin is responsible for the formation of new arteries and veins from pre-existing blood vessels, a process known as angiogenesis. This process includes sprouting, endothelial cell migration, proliferation, and vascular instability and stabilization.
Angiopoietins are responsible for the assembly and disassembly of the endothelial lining of blood vessels and work operationally by affecting microvascular permeability, vasodilation or constriction.
The four known angiopoietins are ANGPT1, ANGPT2, ANGPTL3, and ANGPT4. In addition, there are many other proteins related to angiopoietins. ANGPT1 is critical for vascular maturation, adhesion, migration, and survival. In contrast, ANGPT2 promotes cell death and disrupts vascularization. When ANGPT2 works together with vascular endothelial growth factor (VEGF), it can also promote the formation of new blood vessels.
Structure and mechanism of action
The structure of angiopoietins includes an N-terminal super-integrated domain, a central curved domain, a linker region, and a C-terminal cellulose-associated domain, which is the key to the binding of ligand to receptor. For example, angiopoietin-1 encodes a 498 amino acid polypeptide with a molecular weight of 57 kDa, while angiopoietin-2 encodes a 496 amino acid polypeptide.
Signaling pathways
The effects of angiopoietin are mainly achieved through two signaling pathways: Tie1 and Tie2. When angiopoietins interact with receptor tyrosine kinases (RTKs), they can trigger the phosphorylation of specific tyrosines and promote the activation of intracellular enzymes. This process is critical for maintaining the integrity and function of blood vessels.
Impact on cancerTie-2 signaling can activate β1-integrin and N-cadherin, promoting the interaction between stem cells and the extracellular matrix, thereby maintaining long-term regenerative capacity.
For cancer, especially small cell and non-small cell lung cancer, ANGPT2 expression levels change as the cancer progresses, making it a potential biomarker. Studies have shown that antibodies that block angiopoietin-2 can significantly reduce the metastasis of cancer cells. This discovery provides new ideas for cancer biomarkers and treatments.
Clinical Relevance
Dysregulation of angiopoietin is a common finding in common blood diseases, such as diabetes and sepsis. Especially in the setting of sepsis, elevated angiopoietin-2 may indicate that the patient is at risk for developing amyloidosis. Clinically, early angiopoietin-2 is also considered a marker for heart disease.
Research on angiopoietin has shown its potential value in cancer treatment. With the regulation of angiogenesis, strategies to suppress tumor proliferation are becoming increasingly important.
In summary, angiopoietins play key roles in regulating angiogenesis, and their signaling interactions have important impacts on biology and clinical medicine both in health and disease. Have you ever wondered whether future cancer treatments might rely more on the secret language of blood vessels?
