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

Author:

McLaughlin Kelsey12,Nadeem Lubna2,Wat Jovian2,Baczyk Dora2,Lye Stephen J.234,Kingdom John C.23

Affiliation:

1. Division of Cardiology, Department of Medicine, Sinai Health System, University of Toronto, Toronto, Canada

2. The Centre for Women’s and Infant’s Health at the Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Canada

3. Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynaecology, Sinai Health System, University of Toronto, Toronto, Canada

4. Department of Physiology, University of Toronto, Toronto, Canada

Abstract

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. The objective of the current investigation was to determine the mechanisms by which LMWH mediates the extracellular release of PlGF from endothelial cells. Cultured human aortic endothelial cells (HAECs) and human umbilical vein endothelial cells (HUVECs) were exposed to LMWH; PlGF transcription, translation, mobilization, and secretion were then assessed. LMWH significantly increased the release of PlGF from both HAECs 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. 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.NEW & NOTEWORTHY There are few therapeutic options available for the prevention of preeclampsia, a serious hypertensive disorder of pregnancy. Women who subsequently develop preeclampsia exhibit significantly reduced circulating levels of the proangiogenic placental growth factor protein. Low molecular weight heparin (LMWH) has previously been investigated as a preventative therapy against the development of preeclampsia; however, its mechanism of action is not known. The current study determined that LMWH promotes the transcription and release of placental growth factor protein from endothelial cells, providing a mechanistic basis by which LMWH could reduce the risk of preeclampsia or minimize disease severity.

Funder

Gouvernement du Canada | CIHR | Institute of Health Services and Policy Research

Alva Foundation

Rose Torno Chair

Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario

Publisher

American Physiological Society

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

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