De novo synthesis of phospholipase A 2 and prostacyclin production by proliferating rat smooth muscle cells

Abstract

We investigated the role of phospholipase A 2 (PLA 2) in cell cycle-dependent alterations of endogenous prostacyclin (PGI 2) syntehsis in aortic smooth muscle cells in culture (VSMC) from Wistar Kyoto rats. Randomly cycling VSMC generated more PGI 2 than the stationary cells. Cell cycle analysis showed that PGI 2 production capacity was increased from the G0/G1 through the early DNA synthetic (S) phases. Enzyme analysis revealed that, although there were different mechanisms underlying this increase in the PGI 2 production during the G0/G1, the peak at 4 hours coincided with a sharp increase in PLA 2 activity. This increase in PLA 2 activity was preceded by an increased expression of functional PLA 2 messenger RNA, and protein synthesis inhibition prevented most of the increase in PGI 2 production at 4 hours. These data indicate that endogenous PGI 2 generation is mainly increased during the G0/G1 period and that this event is secondary to de novo synthesis of PLA 2 and probably, at least in part, to cyclooxygenase induction. This mechanism provides a negative feedback regulating VSMC proliferation.