Angiopoietin

Family of growth factors involved in angiogenesis

Angiopoietin structure

Angiopoietins are a family of growth factors that play a critical role in the development and maintenance of the vascular system. They are involved in the process of angiogenesis, which is the formation of new blood vessels from pre-existing ones. Angiopoietins are primarily known for their interactions with the Tie receptors, particularly Tie2, which is a receptor tyrosine kinase.

Structure

Domain structure of angiopoietin

Angiopoietins are secreted proteins that share a common structure consisting of an N-terminal super clustering domain, a central coiled-coil domain, and a C-terminal fibrinogen-like domain. The fibrinogen-like domain is responsible for binding to the Tie2 receptor, which is crucial for their function in angiogenesis.

Types

There are four known angiopoietins: Angiopoietin-1 (Ang1), Angiopoietin-2 (Ang2), Angiopoietin-3 (Ang3), and Angiopoietin-4 (Ang4). Each of these has distinct roles in vascular development and function:

• Angiopoietin-1 (Ang1): Primarily acts as an agonist for the Tie2 receptor, promoting blood vessel maturation and stability. It is essential for maintaining the quiescence and integrity of blood vessels.

• Angiopoietin-2 (Ang2): Functions as a context-dependent antagonist or agonist of Tie2. It is involved in vascular remodeling and destabilization, often acting in opposition to Ang1. Ang2 is upregulated in response to hypoxia and inflammation.

• Angiopoietin-3 (Ang3) and Angiopoietin-4 (Ang4): These are less well-characterized but are believed to have similar roles in vascular biology, with species-specific differences in function.

Function

Angiopoietins are critical regulators of blood vessel formation and stability. They work in concert with other growth factors such as vascular endothelial growth factor (VEGF) to coordinate the complex process of angiogenesis. Ang1 and Ang2 have opposing roles, with Ang1 promoting vessel maturation and Ang2 facilitating vascular remodeling and permeability.

Clinical Significance

Dysregulation of angiopoietin signaling is implicated in various pathological conditions, including cancer, diabetic retinopathy, and inflammatory diseases. Therapeutic targeting of angiopoietin pathways is an area of active research, with potential applications in treating these diseases by modulating angiogenesis.

Related pages

• Angiogenesis
• Vascular endothelial growth factor
• Tie receptors