Placenta growth factor and vascular endothelial growth factor a have differential, cell-type specific patterns of expression in vascular cells

Abstract

Objective: PLGF, a VEGF-A related protein, mediates collateral enlargement via monocytes but plays little role in capillary proliferation. In contrast, VEGF-A mediates both collateral enlargement and capillary proliferation. PLGF has been less thoroughly studied than VEGF-A, and questions remain regarding its regulation and function. Therefore, our goal was to characterize the expression of PLGF by vascular cells. We hypothesized that vascular SMC would express more PLGF than EC, since VEGF-A is primarily expressed by non-EC.

Methods: We compared PLGF and VEGF-A across eight EC and SMC lines, then knocked down PLGF and evaluated cell function. We also assessed the effect of hypoxia on PLGF expression and promoter activity.

Results: PLGF was most highly expressed in EC, whereas VEGF-A was most highly expressed in SMC. PLGF knockdown did not affect EC number, migration, or tube formation, but reduced monocyte migration toward EC. Monocyte migration was rescued by exogenous PLGF. Hypoxia increased PLGF protein without activating PLGF gene transcription.

Conclusions: PLGF and VEGF-A have distinct patterns of expression in vascular cells. EC derived PLGF may function primarily in communication between EC and circulating cells. Hypoxia increases EC PLGF expression posttranscriptionally.

Keywords: arteriogenesis; endothelial cells; growth factors; vascular smooth muscle cells.