A POSSIBLE MECHANISM FOR THE STIMULATION OF METALLOPROTEINASE PRODUCTION IN HUMAN AORTIC INTIMAL SMOOTH-MUSCLE CELLS BY LINOLEIC-ACID HYDROPEROXIDE

To approach the mechanism of the stimulating effect of linoleic acid h ydroperoxide on the production of matrix metalloproteinases (MMPs) in human aortic intimal smooth muscle cells (ISMC), we investigated the e ffect of the hydroperoxide on the cytosolic level of Ca2+. Linoleic ac id hydroperoxide provoked an increase in the cytosolic Ca2+ level, but it had no effect on the level of inositol phosphates (IPs) in these c ells, in contrast with the effect of platelet-derived growth factor (P DGF), which elevated the level of both Ca2+ and IPs in these cells. A2 3187, a calcium ionophore, stimulated ISMC to produce matrix prometall oproteinase 1. These results indicate that linoleic acid hydroperoxide stimulates the production of MMPs in ISMC by elevation of the cytosol ic Ca2+ level without the intervention of IPs. In addition, we found t hat the hydroperoxide has no effect on the binding of PDGF to its spec ific receptor on ISMC. (C) 1996 Academic Press. Inc.