Changes in expression of VE-cadherin and MMPs in endothelial cells: Implications for angiogenesis

The ability of ECs (endothelial cells) and their supporting cellular elements to modify their immediate surrounding extracellular matrix (ECM) responding to multiple signals received from the environment is critically important during angiogenesis [1,2]. Both cell-cell and cell-matrix interactions are crucial in the transition of endothelial cell phenotype associated with angiogenesis [3,4]. These interactions are governed by changes in both cell surface receptor for matrix proteins and the nature of the ECM. Matrixmetalloproteinases (MMPs), by virtue of their ability to degrade components of the ECM can influence these processes by altering the composition and structural organization of the ECM, thereby altering matrix-derived signals [1]. Tight regulation of the activity of MMP is required during angiogenesis as excessive proteolysis can cause unwanted damage to the cells and might dissolve the matrix, cell adhesion molecules and receptors needed for anchoring the migrating cells and for the maturation of the neo-vessel [1,5].A temporal relation between the production of MMPs and the onset of angiogenesis has been reported [6]. Down regulation of MMP-2 and MMP-9 under conditions where human umbilical vein endothelial cells (HUVECs) undergo morphological changes to form tubular network-like structure and higher levels of these enzymes under conditions where cell-cell contact was less and formation of such structures did not occur, suggest that down regulation of MMP production by endothelial cells is crucial to angiogenic process [6]. Further, MMPs have been reported to alter with change in endothelial cell shape where maximum activity was reported when the cells were spherical in shape [7].Apart from MMPs, cell adhesion molecules are also equally important regulators of angiogenesis. They form intercellular junctions between endothelial cells, which give the endothelium the ability to control the passage of solutes and circulating cells [8] and endothelial surface