Angiopoietin Family

Angiopoietins: Key Players in Angiogenesis and Vascular Stability

Angiopoietin is a class of proteins closely related to angiogenesis and vascular stability. The angiopoietin family includes Angiopoietin-1 (Ang-1), Angiopoietin-2 (Ang-2), Angiopoietin-3 (Ang-3) and Angiopoietin-4 (Ang-4). These proteins play an important role in blood vessel development, repair and remodeling.

Angiogenin mainly regulates the biological behavior of vascular endothelial cells by interacting with the Tie receptor family. After Ang-1 binds to Tie-2 receptors, it promotes the proliferation, migration and stability of vascular endothelial cells, and contributes to the normal development and maturation of blood vessels. In contrast, Ang-2 is an angiopoietin antagonist, which inhibits the activity of Tie-2 signaling pathway after binding to Tie-2 receptor, leading to the instability of vascular endothelial cells and the increase of vascular permeability.

Angiogenin plays an important clinical role in a variety of physiological and pathological conditions. In embryonic development, angiogenin participates in the formation and differentiation of new blood vessels to ensure the normal blood supply of embryonic organs. In adults, angiogenin plays a key role in vascular repair and regeneration, contributing to wound healing and tissue regeneration. In addition, angiogenin is also closely related to tumor angiogenesis, and high-level Ang-2 expression is closely related to tumor angiogenesis, metastasis and prognosis.

Based on the important biological functions of angiogenin, researchers are exploring the use of angiogenin as a target for the treatment of vascular-related diseases. Several studies have shown that modulating the expression and activity of the angiopoietin family can improve the therapeutic effect of diseases such as cardiovascular diseases, tumors and inflammatory diseases. Therefore, angiopoietin and its receptors are important targets for potential drug development and therapeutic strategies.

Tie Receptor: Angiopoietin Signaling and Vascular Maintenance

Angiopoietin receptor Tie is a member of the tyrosine kinase family and can be divided into two subtypes, Tie- and Tie-2. Tie-1 was first isolated from the human chronic myeloid leukemia K562 cell line, and it is mainly related to the fluid exchange of capillaries and the response of blood vessels to hemodynamic effects. No ligands binding to Tie-1 have been found yet, Tie-2 is the receptor of Ang, which is mainly expressed in vascular endothelial cells in embryonic period and pulmonary vessels, follicles, wound granulation tissue and other angiogenesis active vascular endothelial cells in embryonic period, and plays a role after phosphorylation with Ang. Involved in regulating the ability of endothelial cells to recruit surrounding stromal cells and maintaining vascular integrity.

The Angiopoietin-Tie-2 Signaling Pathway: Regulation of Vascular Endothelial Cell Behavior

The Angiopoietin signaling pathway plays a crucial role in regulating the biological behavior of vascular endothelial cells through its interaction with the receptor Tie-2 (Tunica interna endothelial-2), thereby influencing angiogenesis and vascular stability. The pathway involves several key steps:

1. Binding and Activation: Angiopoietin binds to the Tie-2 receptor via its specific domain, triggering the activation of the Tie-2 receptor's tyrosine kinase activity.
2. Kinase Activation: Upon activation, the Tie-2 receptor transmits signals through autophosphorylation or mutual phosphorylation, activating downstream signaling molecules.
3. Downstream Signaling: Activated Tie-2 receptors initiate multiple signaling pathways, including the PI3K (phosphatidylinositol 3 kinase)-Akt (protein kinase B) pathway, Ras-MAPK (mitogen-activated protein kinase) pathway, JAK (Janus kinase)-STAT (signal transducer and activator of transcription) pathway, among others.
4. Cellular Physiological Effects: Activation of the aforementioned signaling pathways leads to various physiological effects in vascular endothelial cells, such as increased cell survival, promotion of cell proliferation and migration, and enhancement of vascular endothelial cell tight junctions, ultimately contributing to vascular stability.

Clinical Applications of Angiopoietin

Angiopoietin holds significant clinical importance, with notable applications in various areas:

1. Angiogenesis and Tissue Repair: Angiopoietin regulates the behavior of vascular endothelial cells and facilitates angiogenesis and tissue repair through its interaction with the receptor Tie-2. This pivotal role makes angiopoietin a valuable tool for promoting the formation of new blood vessels and enhancing tissue blood supply. It shows potential for treating conditions like trauma, ischemic diseases, and cardiovascular diseases.
2. Tumor Therapy: Angiopoietin is involved in tumor angiogenesis, growth, and metastasis. Inhibiting angiopoietin's function can impede tumor angiogenesis, leading to the inhibition of tumor growth and metastasis. Consequently, angiopoietin and its receptor Tie-2 have emerged as potential targets for anti-tumor therapy, with ongoing research and drug development endeavors.
3. Circulatory Diseases: Angiopoietin plays a crucial role in maintaining the stability and functionality of blood vessel walls. Abnormal expression or dysfunction of angiopoietin is associated with various circulatory diseases, such as atherosclerosis, hypertension, and diabetes. Investigating the mechanisms and regulatory pathways of angiopoietin in these diseases holds promise for the development of diagnostic and therapeutic methods.

Summary of Angiopoietin Family

In summary, angiogenin plays an important role in regulating angiogenesis, maintaining vascular homeostasis, and being associated with various diseases. Further research on the function and regulation mechanism of angiogenin will help to deeply understand the mechanism of angiogenesis, and provide new ways and strategies for the treatment and drug development of related diseases.

Angiopoietin

Angiopoietin Receptor

References:

[1] Saharinen, P., Eklund, L. & Alitalo, K. Therapeutic targeting of the angiopoietin–TIE pathway. Nat Rev Drug Discov 16, 635–661 (2017). https://doi.org/10.1038/nrd.2016.278