What is Endostatin?
Angiogenesis is the formation of new capillaries from preexisting blood vessels. Endostatin is a 20-kDa C-terminal fragment of collagen XVIII that plays a key role as an angiogenesis inhibitor and consists of 183-184 amino acid residues (its molecular weight is 20 kD). As a potent inhibitor of angiogenesis, endostatin has been found in recent studies to activate a series of signaling pathways thereby inducing endothelial cell apoptosis. It binds to numerous membrane proteins including integrins and heparin sulfate and this binding is further evidence of this biomarker’s involvement with multiple signaling pathways in regards to angiogenesis. In addition, other functions of endostatin in relation to cell death processes include roles in reducing cell migration, adhesion, and proliferation.
Endostatin is generated by proteoltyic cleavage by proteases or matrix metalloproteinases (MMPs) (MMPs have a variety of actions influencing fibrinolysis and angiogenesis). It is localized in the vascular basement membrane zones in various organs. Following the proteolysis, once endostatin is formed it can either stay attached to basement membranes (immobilized) or be released into circulation (soluble). Research has demonstrated that both forms of endostatin have unique biological activities. These activities at the molecular level are still being studied but thus far, it has been discovered that endostatin in combination with angiogenic factors, have an integral role in endothelial response to tissue damage such as renal injury.
Reasons to Measure Endostatin
Endostatin is a vital component for angiogenesis which is necessary for numerous pathological functions, therefore it has been indicated in a vast variety of diseases and other medical conditions. Measuring endostatin can provide remarkable value for detecting and monitoring diseases/conditions, predicting disease risk, and offering a new target for multiple therapies in related areas of research.
Endostatin has been associated with many diseases such as:
- Chronic Kidney Disease (CKD)
- Renal Microvascular Disease
- Idiopathic Pulmonary Fibrosis (IPF)
- Bellini MH et al. “Immobilized Kidney 28-kDa Endostatin-Related (KES28kDa) Fragment Promotes Endothelial Cell Survival.” Bellini MH et al., Am J Nephrol, 2010; 31(3):255-61.
- Chen J et al. Elevated Plasma Levels of Endostatin are Associated with Chronic Kidney Disease”. Am J Nephrol, 2012; 35(4): 335-40.
- Faye, Clement et al. “The First Draft of the Endostatin Interaction Network.”The Journal of Biological Chemistry 2009; 284, 22041-22047.
- Iqbal CW et al. “Early-onset Coronary Artery Disease After Pediatric Kidney Transplantation: Implicating the Angiogenesis Inhibitor, Endostatin.”. Am Surg, 2011; 77(6): 731-5.
- Nyberg, Pia et al. “Endogenous Inhibitors of Angiogenesis.” Cancer Res 2005; 65: (10).
- Rehn, Marko et al. “Interaction of Endostatin with Integrins Implicated in Angiogenesis.” PNAS, 2001; 98: 1024–1029, 2001.
- Richter et al. “Soluble Endostatin is a Novel Inhibitor of Epithelial Repair in Idiopathic Pulmonary Fibrosis.” Thorax 2009;64:156–161.
- Sodha NR et al. “Endostatin and angiostatin are increased in diabetic patients with coronary artery disease and associated with impaired coronary collateral formation.” Am J Physiol Heart Circ Physiol, 2009; 296: H428 – H434.