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Old molecule, new use - researchers show how heparin can help prevent preeclampsia

February 02, 2017

 

by Meghan Krizus 

Low Molecular Weight Heparin Improves Endothelial Function in Pregnant Women at High Risk of Preeclampsia

From the early work of Dr. Charles Best to the present, Toronto researchers have taken a keen interest in how heparin may be used to treat human disease. Most often used for its anticoagulant properties, recent discoveries have shown how this molecule can treat cardiovascular disease in other ways. Now, in a collaborative effort by researchers at the LTRI, scientists have demonstrated how a form of heparin known as low molecular weight heparin (LMWH) can improve cardiovascular function in women at high risk of preeclampsia.

Preeclampsia, a dangerous complication in pregnancy, is characterized by cardiovascular abnormalities that when left untreated can prove fatal to both mother and fetus. Moreover, as preeclampsia remains difficult to treat and not fully understood, new tools are needed to detect onset of preeclampsia, and, ideally, to prevent it from developing in the first place.

From left to right, authors Dr. John Parker, Dr. Kelsey McLaughlin, and Dr. John Kingdom.  
Authors: Dr. John Parker, Dr. Kelsey McLaughlin, and Dr. John Kingdom.  
LMWH has been previously used as a way to prevent preeclampsia in high-risk women; however, there is disagreement as to whether it is effective or valuable as preventative treatment, nor is there full understanding of how it works. With these issues its focus, a new study in Hypertension, spearheaded by LTRI trainee Dr. Kelsey McLaughlin and two of the LTRI’s clinician scientists, Drs. John Kingdom and John Parker, sheds new light on how heparin can improve cardiovascular function. By exploring under which conditions it may be a useful tool in preventing preeclampsia from developing in high-risk women, the authors aimed to provide evidence for targeted and responsible use of an expensive medicine.

Combining both in vivo and in vitro methods, the team demonstrated how LMWH modifies cardiovascular function at the molecular level. They noted that LMWH can change the function of the endothelium (the cells that make up the inner lining of blood vessels) by influencing the secretion of pro-angiogenic proteins which are molecules that promote formation of blood vessels.

Using human umbilical vein endothelial cells (HUVECs) as a model for endothelial function in vitro, the authors noted that after exposing these cells to patient serum and LMWH, levels of two growth factors termed PlGF-1 and PlGF-2 within the cells decreased, while the secretion of these proteins increased. They also supported this finding in vivo, showing that LMWH increased levels of PlGF in the plasma of high-risk patients randomized to LMWH, but not those randomized to placebo.

Moreover, the authors also demonstrated that one of the signs of cardiovascular dysfunction in women at risk of preeclampsia is comparatively low levels of PlGF in circulation. Thus, the ability of LMWH to change PlGF secretion may explain how LMWH can suppress preeclampsia in susceptible women: by stimulating the secretion of pro-angiogenic proteins, thus modifying endothelial function and, as a result, cardiovascular function. This, in turn, may pave the way for physicians to understand the conditions under which LMWH should be used clinically.

Citing the importance of Mount Sinai Hospital’s specialized Placenta Clinic, Dr. Kingdom stresses the important role of these clinics. He emphasizes that this specialization allows researchers to access and study select groups of patients sharing the same predisposition to conditions such as preeclampsia, and to develop tools targeted to the patients who will benefit most from them.

Both Dr. Kingdom and co-author Dr. McLaughlin highlight how this innovation is the product cooperation between disciplines. Describing her work as a part of “a very collaborative field,” Dr. McLaughlin pinpoints how novel collaborations between Cardiology and Women’s and Infants’ Health, and within the LTRI, produces important results with immediate relevance to patient care.

So what are the next steps for what Dr. Kingdom describes as “a flagship enterprise respected around the world”? According to the authors, more research is already underway. As just a small part of their ongoing efforts, their group is already working with pharmaceutical partners to hone the beneficial effects of LMWH. They aim to explore the properties and effects of a truncated form of heparin, research that surely promises to have an impact on women’s and infants’ health in the years to come.

 

Want to know more about preeclampsia, LMWH, and women’s and infants’ health? There are many resources to help you, especially at Mount Sinai Hospital:

 

Learn about our facilities here at Mount Sinai Hospital, and our team of dedicated researchers:

 

 

 

 

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