Angiopoietin

Angiopoietin is part of a family of vascular growth factors that play a role in embryonic and postnatal angiogenesis. Angiopoietin signaling most directly corresponds with angiogenesis, the process by which new arteries and veins form from preexisting blood vessels. Angiogenesis proceeds through sprouting, endothelial cell migration, proliferation, and vessel destabilization and stabilization. They are responsible for assembling and disassembling the endothelial lining of blood vessels. Angiopoietin cytokines are involved with controlling microvascular permeability, vasodilation, and vasoconstriction by signaling smooth muscle cells surrounding vessels. There are now four identified angiopoietins: ANGPT1, ANGPT2, ANGPTL3, ANGPT4. Angiopoietin is part of a family of vascular growth factors that play a role in embryonic and postnatal angiogenesis. Angiopoietin signaling most directly corresponds with angiogenesis, the process by which new arteries and veins form from preexisting blood vessels. Angiogenesis proceeds through sprouting, endothelial cell migration, proliferation, and vessel destabilization and stabilization. They are responsible for assembling and disassembling the endothelial lining of blood vessels. Angiopoietin cytokines are involved with controlling microvascular permeability, vasodilation, and vasoconstriction by signaling smooth muscle cells surrounding vessels. There are now four identified angiopoietins: ANGPT1, ANGPT2, ANGPTL3, ANGPT4. In addition, there are a number of proteins that are closely related to ('like') angiopoietins (Angiopoietin-related protein 1, ANGPTL2, ANGPTL3, ANGPTL4, ANGPTL5, ANGPTL6, ANGPTL7, ANGPTL8). Angiopoietin-1 is critical for vessel maturation, adhesion, migration, and survival. Angiopoietin-2, on the other hand, promotes cell death and disrupts vascularization. Yet, when it is in conjunction with vascular endothelial growth factors, or VEGF, it can promote neo-vascularization. Structurally, angiopoietins have an N-terminal super clustering domain, a central coiled domain, a linker region, and a C-terminal fibrinogen-related domain responsible for the binding between the ligand and receptor. Angiopoietin-1 encodes a 498 amino acid polypeptide with a molecular weight of 57 kDa whereas angiopoietin-2 encodes a 496 amino acid polypeptide. Angiopoietin-1 and angiopoietin-2 can form dimers, trimers, and tetramers. Angiopoietin-1 has the ability to form higher order multimers through its super clustering domain. However, not all of the structures can interact with the tyrosine kinase receptor. The receptor can only be activated at the tetramer level or higher. The collective interactions between angiopoietins, receptor tyrosine kinases, vascular endothelial growth factors and their receptors form the two signaling pathways— Tie-1 and Tie-2. The two receptor pathways are named as a result of their role in mediating cell signals by inducing the phosphorylation of specific tyrosines. This in turn initiates the binding and activation of downstream intracellular enzymes, a process known as cell signaling. Tie-2/Ang-1 signaling activates β1-integrin and N-cadherin in LSK-Tie2+ cells and promotes hematopoietic stem cell (HSC) interactions with extracellular matrix and its cellular components. Ang-1 promotes quiescence of HSC in vivo. This quiescence or slow cell cycling of HSCs induced by Tie-2/Ang-1 signaling contributes to the maintenance of long-term repopulating ability of HSC and the protection of the HSC compartment from various cellular stresses. Tie-2/Ang-1 signaling plays a critical role in the HSC that is required for the long-term maintenance and survival of HSC in bone marrow. In the endosteum, Tie-2/Ang-1 signaling is predominantly expressed by osteoblastic cells. Although which specific TIE receptors mediate signals downstream of angiogenesis stimulation is highly contested, it is clear that TIE-2 is capable of activation as a result of binding angiopoietins. Angiopoietin proteins 1 through 4 are all ligands for Tie-2 receptors. Tie-1 heterodimerizes with Tie-2 to enhance and modulate signal transduction of Tie-2 for vascular development and maturation. Tyrosine kinase receptors are typically expressed on vascular endothelial cells and specific macrophages for immune responses. Angiopoietin-1 is a growth factor produced by vascular support cells, specialized pericytes in the kidney, and hepatic stellate cells (ITO) cells in the liver. This growth factor is also a glycoprotein and functions as an agonist for the tyrosine receptor found in endothelial cells. Angiopoietin-1 and tyrosine kinase signaling are essential for regulating blood vessel development and the stability of mature vessels.