ANGPT - Angiopoietin |Elisa - Clia - Antibody - Protein

Background:

ANGPT or Angiopoietin is a family of proteins involved in the regulation of angiogenesis. Angiopoietins play a crucial role in the development of blood vessels and are essential for maintaining the integrity of the vascular system. There are four known members of the Angiopoietin family: Angiopoietin-1 (ANGPT1), Angiopoietin-2 (ANGPT2), Angiopoietin-3 (ANGPT3), and Angiopoietin-4 (ANGPT4). Among these, ANGPT1 and ANGPT2 are the most well-studied. Angiopoietin-1 (ANGPT1) is protein is mainly produced by pericytes, smooth muscle cells surrounding blood vessels. It binds to the receptor Tie-2 on endothelial cells (cells lining the inside of blood vessels), promoting blood vessel stabilization, maturation, and integrity. ANGPT1 is critical for maintaining the quiescent, or resting, state of blood vessels. Angiopoietin-2 (ANGPT2) is produced by endothelial cells themselves and acts as a competitive antagonist of Tie-2. This means that when ANGPT2 is present, it can interfere with ANGPT1/Tie-2 signaling, leading to destabilization of blood vessels. ANGPT2 is often associated with angiogenesis, inflammation, and vascular permeability. It's released during times of stress or injury and can promote the growth of new blood vessels. Together, ANGPT1 and ANGPT2 help to regulate the process of angiogenesis, which is crucial for various physiological processes, including wound healing, embryonic development, and the menstrual cycle. Dysregulation of angiopoietins and their receptors is associated with several diseases, including cancer, cardiovascular diseases, and inflammatory condition

Protein Structure:

• Primary Structure: Angiopoietins are secreted glycoproteins. They have an N-terminal signal peptide, a coiled-coil domain, a fibrinogen-like domain, and a C-terminal domain responsible for receptor binding.
• Tertiary Structure: The fibrinogen-like domain is critical for receptor binding and biological activity.
• Quaternary Structure: Angiopoietins can form multimers, with ANGPT1 often forming dimers or trimers, which are essential for its full biological activity.

Classification and Subtypes:

• ANGPT1: Promotes vascular maturation and stability, reduces vascular permeability.
• ANGPT2: Acts as an antagonist or partial agonist of ANGPT1, context-dependent, and can promote angiogenesis and vascular permeability in the presence of VEGF.
• ANGPT3 and ANGPT4: Less well-studied, with roles in lymphangiogenesis and angiogenesis respectively, and showing tissue-specific expression patterns.

Function and Biological Significance:

• Vascular Development: Angiopoietins are crucial for blood vessel maturation and stabilization. ANGPT1, in particular, promotes interactions between endothelial cells and surrounding support cells.
• Angiogenesis: ANGPT2 facilitates angiogenesis in the presence of VEGF by destabilizing blood vessels, making them more responsive to VEGF signaling.
• Vascular Permeability: ANGPT2 increases vascular permeability, which can be beneficial for processes like inflammation and tissue repair but can contribute to pathological conditions if unregulated.

Interactions:

• Tie2 Receptor: The primary receptor for angiopoietins. ANGPT1 activates Tie2, promoting vessel stability and anti-inflammatory effects. ANGPT2 can bind Tie2 and inhibit its activation or act as an agonist under certain conditions.
• Integrins: Angiopoietins interact with integrins on endothelial cells, influencing cell adhesion and migration.
• VEGF: Vascular Endothelial Growth Factor (VEGF) works synergistically with angiopoietins to regulate blood vessel formation and function.

Clinical Issues:

• Cancer: Dysregulated expression of angiopoietins, particularly ANGPT2, is associated with tumor angiogenesis and metastasis. High levels of ANGPT2 are often found in various cancers and correlate with poor prognosis.
• Diabetic Retinopathy: ANGPT2 is implicated in increased vascular permeability and neovascularization in diabetic retinopathy.
• Inflammatory Diseases: Elevated ANGPT2 levels are associated with inflammatory conditions, where it contributes to vascular leakage and inflammation.
• Therapeutic Potential: Therapeutic targeting of angiopoietins and their pathways is under investigation for cancer treatment, diabetic retinopathy, and other conditions characterized by pathological angiogenesis and vascular leakage.

Summary:

Angiopoietins are key regulators of angiogenesis and vascular homeostasis. They interact primarily with the Tie2 receptor, influencing vascular stability, permeability, and endothelial cell function. ANGPT1 generally promotes vessel maturation and stability, while ANGPT2 has more complex roles, acting as both an antagonist and agonist of ANGPT1 in different contexts. Dysregulation of angiopoietins is linked to various pathological conditions, including cancer, inflammatory diseases, and diabetic retinopathy. Understanding the precise roles and mechanisms of angiopoietins in vascular biology is crucial for developing therapeutic strategies targeting these pathways.