Purchase this article with an account.
A. Kazlauskas, A. Venkatakrishnan, E. Im; Cathepsin B Regulates the Intrinsic Angiogenic Threshold of Endothelial Cells . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4181.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: The lysosomal protease cathepsin B has been implicated in a variety of pathologies including pancreatitis, tumor angiogenesis and neuronal diseases. Cathepsin B is expressed in various regions of eye, including retina. However, there are no reports investigating cathepsin B in retinal or choroidal angiogenesis. The purpose of this study was to investigate the role of cathepsin B in angiogenesis. Methods:We used primary bovine retinal endothelial cells in an in vitro angiogenesis (tube formation) assay. VEGF protein level was measured by ELISA. The levels of endostatin, and HIF–1α were measured by Western blotting. Results: When cultured between two layers of collagen I, primary endothelial cells formed tubes in response to exogenously added VEGF. Overexpressing cathepsin B reduced the VEGF–dependent tube response, whereas pharmacologically or molecularly suppressing cathepsin B eliminated the dependence on exogenous VEGF. However, tube formation still required VEGF receptor activity, which suggested a role for endogenous VEGF. Indeed, blocking cathepsin B activity increased the level of endogenous VEGF, and HIF–1α. In addition to boosting the level of pro–angiogenic factors, blocking cathepsin B activity reduced the amount of the anti–angiogenic protein endostatin. Conclusions: Thus endothelial cells have the intrinsic capacity to contribute to the overall balance of pro– and anti–angiogenic agents. These observations complement and expand our appreciation of how proteases such as cathepsin B are capable of regulating angiogenesis, and improve our understanding of endothelial cell biology.
This PDF is available to Subscribers Only