Placenta growth factor gene expression is increased in vascular smooth muscle cells in association with metabolic stress

Abstract

Placenta growth factor (PlGF) is a VEGF‐related protein that is associated with arteriogenesis. We hypothesized that PlGF gene expression in vascular smooth muscle cells (VSMC) would be affected by the presence of endothelial cells (EC) and/or by EC‐derived factors. PlGF mRNA expression was increased in VSMC (N=17) by 24 h of co‐culture with EOMA EC, to 2.67 ± 0.39‐fold of monocultured VSMC level (N=9; p=0.003). Treatment of VSMC with EC‐conditioned culture media (ECM; N=14) for 4 h. also increased PlGF mRNA (to 2.34 ± 0.21 fold of control; N=16, p<0.05). The effect of ECM on PlGF mRNA was transient, since expression was no longer elevated after 24 h. of incubation with ECM (0.85 ± 0.29 fold of control; N=10). Treatment of VSMC with media auto‐conditioned by VSMC also produced a ~2 fold increase in PlGF mRNA. Since the effect was not consistent with the action of a short‐lived endothelial‐specific mediator (such as NO), we next investigated whether metabolic substrates or products might induce PlGF expression. Lactate concentration was 8.17 ± 0.14 mM in EC‐conditioned media (N=14), as opposed to 0.50 ± 0.26 mM in un‐conditioned media (N=8; p<0.001). Lactate correlated with PlGF expression in VSMC after 4 h. of treatment with ECM (R2=0.66; p=0.001). However, exogenous lactate (0–15 mM; N=13) had no effect on PlGF mRNA level in VSMC. These data suggest that PlGF gene expression may be sensitive to glucose deprivation. Support: OSU.