DE-NOVO SYNTHESIS OF PHOSPHOLIPASE-A(2) AND PROSTACYCLIN PRODUCTION BY PROLIFERATING RAT SMOOTH-MUSCLE CELLS

We investigated the role of phospholipase A2 (PLA2) in cell cycle-depe ndent alterations of endogenous prostacyclin (PGI2) synthesis in aorti c smooth muscle cells in culture (VSMC) from Wistar Kyoto rats. Random ly cycling VSMC generated more PGI2 than the stationary cells. Cell cy cle analysis showed that PGI2 production capacity was increased from t he G0/G1 through the early DNA synthetic (S) phases. Enzyme analysis r evealed that, although there were different mechanisms underlying this increase in the PGI2 production during the GO/G1, the peak at 4 hours coincided with a sharp increase in PLA2 activity. This increase in PL A2 activity was preceded by an increased expression of functional PLA2 messenger RNA, and protein synthesis inhibition prevented most of the increase in PGI2 production at 4 hours. These data indicate that endo genous PGI2 generation is mainly increased during the G0/G1 period and that this event is secondary to de novo synthesis of PLA2 and probabl y, at least in part, to cyclooxygenase induction. This mechanism provi des a negative feedback regulating VSMC proliferation.