Angiopoietin-2: A Key Regulator of Vascular Stability and Disease Progression

Molecular Structure and Expression

Angiopoietin-2 (ANG2) is a large glycoprotein that is an angiopoietin which is a protein that contains a coiled-coil domain as well as a fibrinogen like domain. This 496 amino acid residues in length molecule is a partial angiopoietin-1 antagonist and interacts with the TIE2 receptor tyrosine kinase. ANG2 is primarily produced by endothelial cells and stored in organelles called Weibel-Palade bodies. This gene is normally expressed at very low levels under normal conditions, but its expression is up regulated upon exposure to a number of stimuli including hypoxia, inflammation and growth factors.

Physiological Functions in Vascular Biology

In normal vasculature ANG2 plays a very important role in the regulation of vascular tone and the ability of the vessels to change their structure in response to alterations in the environment. While its counterpart ANG1 is a stabilizer of vessels ANG2 is a destabilizer that sets the stage for angiogenic processes. This action is crucial during normal processes including tissue repair, menstrual cycle in women and tissue restoration. ANG2 does this by challenging ANG1 for TIE2 receptor binding and thus plays a role in regulating endothelial cell survival, migration and vessel permeability.

Role in Pathological Angiogenesis

In normal vasculature ANG2 plays a very important role in the regulation of vascular tone and the ability of vessels to change their structure in response to changes in the environment. While its counterpart ANG1 is a stabilizer of vessels ANG2 is a destabilizer that sets the stage for angiogenic processes. This action is crucial in the course of normal processes including tissue repair, menstrual cycle in women and tissue restoration. ANG2 does this by challenging ANG1 for TIE2 receptor binding site hence regulating endothelial cell turnover, movement and vessel permeability. The protein’s capacity to enhance the endothelial cells’ responses to other growth factors including VEGF makes it a master regulator of the vascular functions.

Clinical Significance and Biomarker Potential

ANG2 clinical significance is also increasing due to the discoveries of its potential as a biomarker and target for therapy. It has been observed that increased serum ANG2 level is a negative prognostic factor in many cancers thus making it a useful prognostic factor. In the critical care medicine ANG2 plays a role of endothelial function and disease severity marker in the conditions such as sepsis, ARDS and multiple organ failure. The protein level is associated with the disease process and the outcome which provides the clinicians with a means of patient selection and management. In addition, the Ang2/Ang1 has been identified as a sensitive indicator of vascular integrity and disease.

Therapeutic Targeting and Future Directions

Due to the possibility of utilizing ANG2 it has attracted much attention in the pharmaceutical industry. There are several strategies that are being developed at the moment and these include the use of monoclonal antibodies, peptide inhibitors and combination therapies that include the blocking of ANG2 as well as the VEGF pathways. The clinical trials have revealed quite effective outcomes in the treatment of cancer especially when administered along with other anti-angiogenic therapies. The efforts are also being made to enhance the selectivity and efficiency of ANG2 targeted therapies with the newly designed therapeutic approaches aiming at delivering the therapy to the specific tissues and at specific time intervals.

Suitable ELISA Kits

• Angiopoietin-2 ELISA Kit
• ANG2 ELISA Kit