Hydrogen peroxide-mediated, lysyl oxidase-dependent chemotaxis of vascularsmooth muscle cells

Lysyl oxidase (LO), an enzyme secreted by vascular smooth muscle cells (VSM C), initiates the covalent crosslinking of polypeptide chains within collag en and elastin. The present study reveals that purified LO strongly induces directional migration of VSMC in an in vitro assay system. LO-dependent ch emotaxis, but not chemokinesis, was abolished by beta-aminopropionitrile, a n active site inhibitor of LO, or by catalase, as well as by prior heat den aturation. This indicates that the H2O2 product of amine oxidation by LO is critical to the expression of its chemotactic activity. The results indica te that the chemotactic response requires direct access between LO and a su bstrate molecule (or molecules) tightly associated with the VSMC. The addit ion of LO to VSMC elevated the levels of intracellular H2O2, enhanced stres s fiber formation, and focal adhesion assembly, is consistent with the-indu ction of the chemotactic response. J. Cell. Biochem. 78:550-557, 2000. (C) 2000 Wiley-Liss, Inc.