Angiopoietin 2 (ANGPT2) is a family member of the human ANGPT-TIE system. It is primarily produced by endothelial cells and stored in Weibel-Palade bodies from where it can be rapidly released upon stimulation to act as an autocrine regulator of endothelial cell functions. ANGPT2 plays a key role in angiogenesis. ANGPT2 acts as a vessel destabilizing agent that induces permeability and leads to the dissociation of cell-cell contacts in cultured endothelial cells. In addition, tumor necrosis factor-α (TNF-α)-induced activation of NF-κB can upregulate ANGPT2 expression in human umbilical vein endothelial cells (HUVECs). There are two major isoforms of angiopoietins to regulate vascular homeostasis, namely ANGPT1 and ANGPT2. ANGPTs receptors or co-receptors, such as TIE1 and integrins, could help explain the different context-dependent actions of the ANGPTs.
ANGPT1 is an agonistic ligand of TIE2 (Fig.1). In contrast, ANGPT2 normally functions as an ANGPT1 antagonist and mediates increases in vascular permeability and angiogenesis, but it could also function as a partial TIE2 agonist under certain conditions. TIE1 is activated by activated TIE2 and the extracellular domain of TIE1, in turn, interferes with the ANGPT1-TIE2 interaction and thereby antagonizes ANGPT1. The intracellular domains of TIE2 and vascular endothelial protein tyrosine phosphatase (VEPTP) interact, causing VEPTP to dephosphorylate activated TIE2. ANGPT1 functions as an anti-inflammatory cytokine, whereas ANGPT2 has a pro-inflammatory function. ANGPT1-activated TIE2 recruits ABIN2 (also known as TNIP2), which inhibits NF-κB-mediated inflammatory gene expression, including intercellular adhesion molecule 1, vascular cell adhesion molecule 1, E-selectin and tissue factor, whereas ANGPT2 increases their expression by blocking the function of ANGPT1. In addition, ANGPT2 has been shown to activate β1-integrin, resulting in the destabilization of endothelial cell intercellular junctions via an increase in cell contractility and alteration of pericellular matrix remodeling.
ANGPT2 is an inflammatory cytokine, the circulatory level of which correlates with adverse outcomes in several critical care syndromes, including acute respiratory disease syndrome and sepsis. Recent studies have shown that the overexpression of ANGPT2 correlates with poor prognosis in several cancers. ANGPT2 plays a key role in tumor initiation and increases the number of tumor vessel sprouts, possibly owing to the decreased pericyte coverage and more unstable vessels. In addition, ANGPT2 together with vascular endothelial growth factor (VEGF) have been linked to the polarization of tumor-associated macrophages (TAM). It has been found that in the presence of ANGPT2 and VEGF, the proportion of protumor M2 macrophages is increased. Emerging reports show that ANGPT2 is associated with a greater risk of all-cause and cardiovascular mortality in the general population, with the deterioration of cardiac function in heart failure patients and with higher mortality in myocardial infarction and cardiogenic shock patients. The precise role of ANGPT2 in ischemic heart disease remains poorly elucidated.
Fig.1 The ANGPT2-TIE signaling pathways. (Huang, 2010)
Inhibition of TIE2 receptor signaling via ANGPT2 causes destabilization of the endothelium in most vascular beds and promotes inflammation, vascular leakage, impairment of the endothelial glycocalyx and activation of α5β1 integrin signaling. Creative Biolabs provides a series of ANGPT2 assay portfolio services, including angiogenesis assays (tube formation assay, sprouting assay, additional angiogenesis assays), immunofluorescence and immunohistochemistry, western blotting, ELISA, cell proliferation assay, cell migration and invasion assay, cell adhesion assay, cell apoptosis assay, macrophage polarization assay and so on.
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Reference
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