Amanda de Oliveira Faculty of Medicine & Dentistry
Understanding the higher risk of cardiovascular disease after complicated pregnancies
Researchers are testing an antibody to improve blood vessel function that could help women with pre-eclampsia
Pre-eclampsia is a significant cause of sickness and death for mothers and children worldwide, affecting five to eight per cent of all pregnancies. Additionally, pre-eclampsia doubles the risk of heart disease and stroke for women — their children also have an increased risk of developing cardiovascular diseases later in life.
Unfortunately, we still do not know what causes pre-eclampsia and how it evolves, although we do know that excessive cholesterol increases the risk of this pregnancy complication. During pregnancy, women have higher levels of cholesterol, needed for hormone production as well as growth and development of the baby. However, in some women, cholesterol levels rise too much and this can result in pre-eclampsia.
“I hope that by understanding the underlying mechanisms of pregnancies complicated by excessive cholesterol it will reveal a new way to reduce the burden of pregnancy complications, which consequently will improve the lives of women and children,” says researcher Amanda Almeida de Oliveira, a WCHRI postdoctoral fellow supervised by Sandra Davidge in the Department of Obstetrics & Gynecology.
de Oliveira suspects that a protein of the immune system holds the key to understanding the development of cardiovascular diseases in pregnant women. When this protein, called toll-like receptor 4 (TLR4), is activated on blood vessels, it increases oxidative stress and inflammation, which harms the blood vessels and can lead to cardiovascular disease. However, it is not known if TLR4 is also responsible for problems in the mother's blood vessels during and after pre-eclampsia.
“We believe that pre-eclampsia is associated with increased TLR4 activation in the mother, which continues after the delivery of the baby and impairs the cardiovascular system of these women,” says de Oliveira. She will test animal models of pre-eclampsia (caused by high cholesterol) with an antibody treatment that binds to TLR4 and prevents its activation, to assess whether this improves blood vessel function and pregnancy outcomes. They will also assess the long-term effects of pre-eclampsia in the model by evaluating blood vessel function postpartum.
Cardiovascular diseases are the leading cause of death worldwide and women who had a complicated pregnancy are at an increased risk of having a cardiovascular event. “This project will increase our understanding of pre-eclampsia, and consequently, our ability to design effective treatments against this disorder,” says de Oliveira.
Amanda Almeida de Oliveira is supervised by Sandra Davidge. Her fellowship has been funded by the Stollery Children’s Hospital Foundation and the Alberta Women’s Health Foundation through the Women and Children’s Health Research Institute.