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 hydroperoxide on the production of matrix metalloproteinases (MMPs) in human aortic intimal smooth muscle cells (ISMC), we investigated the effect of the hydroperoxide on the cytosolic level of Ca2+. Linoleic acid hydroperoxide provoked an increase in the cytosolic Ca2+ level, but it had no effect on the level of inositol phosphates (IPs) in these cells, in contrast with the effect of platelet-derived growth factor (PDGF), which elevated the level of both Ca2+ and IPs in these cells. A23187, a calcium ionophore, stimulated ISMC to produce matrix prometalloproteinase 1. These results indicate that linoleic acid hydroperoxide stimulates the production of MMPs in ISMC by elevation of the cytosolic Ca2+ level without the intervention of IPs. In addition, we found that the hydroperoxide has no effect on the binding of PDGF to its specific receptor on ISMC.