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The magic of blood vessels: Why is angiopoietin-1 considered the key to vascular maturation?
In the human body, the formation and maturation of blood vessels play a vital role, especially in various physiological and pathological processes. The angiopoietin series of vascular growth factors, especially angiopoietin-1 (Ang-1), are widely considered to be key factors in promoting vascular maturation. It not only participates in the proliferation and migration of vascular endothelial cells, but also plays an important role in vascular stability and survival.
Members of the angiopoietin family include four known angiopoietins: ANGPT1, ANGPT2, ANGPTL3, and ANGPT4. These factors are involved in the angiogenesis process from embryonic development to postnatal growth.
Angiogenesis, which can be understood as the formation of new blood vessels, depends on a series of complex biological processes. This process involves the migration and proliferation of endothelial cells and the stability and instability of vascular structure. The presence of angiopoietin-1 promotes endothelial cell adhesion and survival, thereby supporting the integrity of vascular structure, which is why it is considered indispensable in many physiological processes.
Structure and function of angiopoietin
Structurally, angiopoietins possess an N-terminal superaggregation domain, a central coiled-coil domain, a linker region, and a C-terminal fibrin-associated domain. These features enable them to bind to specific receptors and activate corresponding signaling pathways. The polypeptide length of angiopoietin-1 is 498 amino acids with a molecular weight of 57 kDa, while angiopoietin-2 consists of 496 amino acids.
The aggregated forms in bubbles, such as dimers, trimers and tetramers, are the only way to activate the receptors. Only tetramers or higher structures can activate tyrosine kinase receptors.
In terms of signal transduction, the effect of angiopoietin is mainly achieved through the Tie-1 and Tie-2 signal transduction pathways. These receptors are expressed on endothelial cells and mediate cell signaling by inducing phosphorylation of specific tyrosine residues, thereby affecting cell function. In this process, Ang-1 can promote the calm state of hematopoietic stem cells, that is, it can maintain the long-term regenerative ability of hematopoietic stem cells and protect these cells from various stresses.
Vascular stability and maturation
Vascular stability and maturation are critical. Angiopoietin-1 allows the connections between endothelial cells to become more stable, thus preventing vascular instability. In addition, when angiopoietin-2 is overexpressed, it may lead to vascular degeneration and death, especially in the absence of other growth factors such as VEGF.
Angiopoietin-2 has been proposed as a biomarker in multiple cancer types, especially in small cell and non-small cell lung cancer, where its expression level is proportional to the stage of cancer.
With the deepening of research, it was found that angiopoietin also showed potential application value in anti-tumor treatment. Angiopoietin-1 and angiopoietin-2 exhibit different mechanisms during tumor growth, and their balance determines tumor progression and metastasis. Regulating angiopoietin is expected to become a new cancer treatment strategy.
Clinical Relevance
Dysregulation of angiopoietin is common in many blood-related diseases, such as diabetes, malaria, sepsis, etc. High expression of angiopoietin-2 is closely associated with poor prognosis and may serve as a biomarker for early diagnosis. In addition, the increase of angiopoietin-2 in cardiovascular disease also shows its significance as a potential biomarker, especially in children with chronic dialysis.
The imbalance between angiopoietin-1 and angiopoietin-2 may lead to the development of various diseases, especially in the process of angiogenesis, and their cooperation and antagonism have attracted much attention in research.
In conclusion, the importance of angiopoietin-1 in vascular maturation and stability cannot be underestimated, especially its potential applications in the fields of cancer and cardiovascular disease are even more exciting. In the face of future research and treatment development, are there other unknown factors that may affect vascular health and stability together with angiopoietin?
