產(chǎn)品概述

Angiopoietin-2 (ANG2) is a 56.9 kDa glycosylated growth factor that is specific for endothelial cells (ECs). ANG2 is expressed in embryonic vessels and contributes to the formation of new vasculature. In adults, it is restricted to sites of vascular remodeling (e.g. ovary, uterus, placenta) and wound healing. ANG2 is regulated by the cytokine vascular endothelial growth factor (VEGF). Together with VEGF, ANG2 induces endothelial cell migration, proliferation, and vascular sprouting. During angiogenesis, ANG2 exerts its effects via the angiopoietin-1/TIE2 receptor signaling system on endothelial cells. Disruption of this signaling leads to the loss of endothelial integrity. In consequence, the endothelium responds to various pro-inflammatory cytokines and growth factors. Thus, ANG2 might cause vascular micro-inflammation in patients with chronic kidney disease (CKD). Various studies demonstrated that ANG2 levels increase with CKD stage and are associated with fluid overload and abnormal cardiac structure. Furthermore, ANG2 concentrations correlate with mortality in patients with CKD stages 4–5. Although ANG2 levels recover after successful kidney transplantation, ANG2 continues to be a cardiovascular risk factor in this population. In cancer, targeting the TIE2-Angiopoietin pathway has shown promising results in some pre-clinical and clinical trials, including studies on recurrent or metastatic breast and renal cell carcinomas. In COVID-19 patients, ANG2 was recently reported to be a relevant factor to predict transfer to the ICU as it was associated with poor lung compliance. Thus, showing that endothelial activation reinforces the hypothesis of a COVID-19-associated microvascular dysfunction. In this context, another study demonstrated that ANG2 levels in critically ill COVID-19 patients correlate with disease severity, hypercoagulation, and mortality. The researchers also provided novel in vivo evidence for a direct role for ANG2 in coagulation through binding to and inhibition of thrombomodulin-mediated anticoagulation. The scientists suggest that inhibition of ANG2 might be beneficial for treating critically ill COVID-19 patients, as well as other patients with hypercoagulation.