Palmitoyl lysophosphatidylcholine mediated mobilization of LPL to the coronary luminal surface requires PKC activation.

Following diazoxide (DZ) induced hypoinsulinemia, cardiac luminal lipoprotein lipase (LPL) increases [Cardiovasc. Res. 3 (2003) 788]. To identify circulating mediators that maintain high LPL in vivo, DZ hearts were perfused for 1 h in the presence or absence of glucose, triglyceride (TG), palmitic acid or palmitoyl lysophosphatidylcholine (PLPC). Only PLPC maintained high luminal LPL in DZ hearts, likely through enzyme recruitment from the cardiomyocyte. PLPC perfusion activated whole heart protein kinase C (PKC) epsilon. As calphostin pretreatment blocked PLPC induced PKC activation, and increases in luminal LPL activity, PKC activation is essential for the effects of PLPC. Incubation of myocytes with PLPC had no effects on either surface or intracellular LPL or PKC suggesting that PKC activation occurs in cells other than the myocyte or that metabolism of PLPC is required for its downstream effects. Since exposure of endothelial cells to PLPC activated PKC, whole heart PKC activation likely occurred in these cells. Incubation of myocytes with LPA, a phospholipase D (PLD) mediated breakdown metabolite of PLPC, significantly enhanced basal and heparin-releasable myocyte LPL activity, an effect that was duplicated by co-incubation of control myocytes with exogenous PLD and PLPC. Our data suggest that at least in the whole heart, the LPL augmenting property of PLPC likely requires endothelial PKC activation, formation of LPA, and mobilization of enzyme from the myocyte to the coronary lumen.