Low molecular weight heparin promotes transcription and release of placental growth factor from endothelial cells

Abstract

Rationale. Circulating levels of placental growth factor (PlGF) are significantly reduced in women who develop preeclampsia. Low molecular weight heparin (LMWH) has been shown to acutely elevate circulating PlGF levels in pregnant women at increased risk of preeclampsia. Objective. The objective of the current investigation was to determine the mechanisms by which LMWH mediates the extracellular release of PlGF from endothelial cells. Methods and Results. Cultured Human Aortic Endothelial Cells (HAEC) and Human Umbilical Vein Endothelial Cells (HUVEC) were exposed to LMWH; PlGF transcription, translation, mobilization and secretion were then assessed. LMWH significantly increased the release of PlGF from both HAEC and HUVECs. LMWH treatment promoted a significant increase of PlGF-1 mRNA expression in HAECs, accompanied by the intracellular transport and release of PlGF into the conditioned media. LMWH-mediated release of PlGF from HAECs was not directly mediated by extracellular mobilization, synthesis or stability of PlGF mRNA / protein. Conclusions. LMWH exposure promotes the release of PlGF from endothelial cells through the upregulation of PlGF-1 mRNA expression. Stimulation of circulating PlGF levels by LMWH may be an important mechanism by which LMWH could reduce the risk of preeclampsia, or minimize disease severity.