rmAng-1, CF (25 UG)

Background: Angiopoietin-1

Angiopoietin-1 (Ang-1) is a secreted glycoprotein that plays a critical role in the development and maintenance of the vascular system (1, 2). It contains a N-terminal coiled-coil region and a C-terminal fibrinogen-like domain separated by a short flexible region (3, 4). Mature Mouse Angiopoietin-1 shares 97% and 98% amino acid sequence identity with Human and rat Angiopoietin-1, respectively. It is expressed by vascular smooth muscle cells and pericytes as an approximately 70 kDa molecule that associates into disulfide-linked homotrimers, tetramers, and pentamers (3, 5). Angiopoietin-1 binds and activates the receptor tyrosine kinase Tie-2, and its association into tetramers is important for full Tie-2 activation (3, 4). Angiopoietin-1 ligation of Tie-2 on vascular endothelial cells (EC) induces the development and branching of blood vessels (6, 7). In sub-confluent EC (i.e. during angiogenesis), Angiopoietin-1 promotes EC motility and Tie-2 localization at the trailing edge of the cell (8). In confluent EC (i.e. in homeostasis), multimeric Angiopoietin-1 enhances vascular integrity by promoting the in trans homotypic association of Tie-2 between EC or with the substratum (8, 9). In addition, Angiopoietin-1 suppresses several VEGF-induced effects on the vasculature including endothelial permeability, stretch-induced release of Angiopoietin-2, and up-regulation of the leukocyte adhesion molecules VCAM-1, ICAM-1, and E-Selectin (10-12). Angiopoietin-1 also interacts with a variety of integrins and the extracellular matrix independently of Tie-2 (13, 14). These interactions support the adhesion, migration and stress resistance of EC, fibroblasts, and myocytes (13, 14). Angiopoietin-1 can protect against pulmonary arterial hypertension (5), reduce the extent of fibrosis and remodeling in infarcted diabetic myocardium (15), and enhance tumor progression and metastasis (16).