Description :
|
Angiopoietin-1 (Ang-1) is a secreted ligand for Tie-2, a tyrosine-kinase receptor expressed primarily on vascular endothelial cells and early hematopoietic cells. Ang-1/ Tie-2 signaling promotes angiogenesis during the development, remodeling, and repair of the vascular system. Transgenic mice lacking expression of either Ang-1 or Tie-2 fail to develop a fully functional cardiovascular system and die before birth. Postnatally, the angiogenic activity of Ang-1/Tie-2 is required during normal tissue repair and remodeling of the female endometrium in the menstrual cycle. Ang-1/Tie-2 signaling appears to be regulated by Angiopoietin-2 (Ang-2), a natural antagonist for Tie-2 that exerts its effects through an internal autocrine loop mechanism. In addition to suppressing endothelial cell activation by inhibiting the expression of adhesion and inflammatory molecules, Ang-1 enhances endothelial cell survival and capillary morphogenesis, and lessens capillary permeability. As such, Ang-1 has a potential to become an effective therapeutic agent for treating various endothelium disorders, including several severe human pulmonary diseases. The efficacy of cell-based Ang-1 gene therapy for acute lung injury (ALI) has recently been studied in a rat model of ALI (1). The results of this study show that such therapy can markedly improve lung condition and suggest that Ang-1 therapy may represent a potential new strategy for the treatment and/or prevention of acute respiratory distress injury (ARDI), a significant cause of morbidity and mortality in critically ill patients. Recombinant human ANG-1, derived from HeLa cells, is a C-terminal histidine tagged glycoprotein which migrates with an apparent molecular mass of 60.0 – 70.0 kDa by SDS-PAGE under reducing conditions. Sequencing analysis shows N-terminal sequences starting with Ser-20 and with Asp-70 of the 498 amino acid precursor protein.
|
