Halifax researcher shows strength of female hearts

Pregnant women’s hearts could hold key to help fight cardiovascular ills

HALIFAX— Women’s hearts might hold the key to the development of new treatments for cardiovascular disease, and Halifax researcher Sarah Wells is leading the investigative charge.

The associate professor in biomedical engineering at Dalhousie University said many people are unaware that during pregnancy, a woman’s heart tissues expand to accommodate the 50 per cent increase in blood flow to support the placenta.

That physical change looks like heart failure in other patients and is a natural phenomenon originally discovered by Wells. In recent years, her work has focused on learning why and how this occurs.

“We’ve known for a long time about this general blood volume increase, and it’s known from ultrasound imaging for instance that women’s hearts and aortas get larger,” Wells said in an interview. “There’s some indication that those changes reverse after birth, but when I looked into the literature, no one had really done any studies on how the tissue was doing this.”

To meet the demands placed on her body to support a fetus, that blood volume increase of nearly 50 per cent happens in the first eight weeks of pregnancy. Wells said this was a fascinating engineering problem.

“I’m interested in heart valves and arteries, tissues that are under constant and very high levels of mechanical loading, nonstop throughout your life, and I’m interested in how they manage to withstand those mechanical loading conditions and not mechanically fail,” she said. “Pregnancy is this … very profound physiological change in your cardiovascular loading conditions and no one had looked at how does the tissue adapt to that biomechanically. That’s what got me on to that project, applying this sort of tissue engineering approach to look at how tissues adapt to changes in mechanical loading conditions.”

For the past eight years, Wells has been looking at the remodelling of cardiovascular tissues in pregnant women, publishing her first paper on the subject in 2012. “We’re still producing results from the lab. There are just so many questions to answer,” she said.

Wells and her collaborators study cattle hearts collected from slaughterhouses and using tissues that are byproducts of the beef industry that would otherwise be discarded. Some of the animals are pregnant at the time of slaughter, others were previously pregnant, and some were never pregnant.

The hearts are big enough that researchers can cut the valves out and take them back to Wells’ mechanical engineering lab. She said until this research, it was thought that heart valves and the large aorta coming off the heart didn’t really adapt or remodel once a person was fully grown. It was believed the only time they experienced any structural and mechanical changes were due to disease.

“What we have shown is that these tissues undergo a remarkable biomechanical adaptation to pregnancy. The heart valves enlarge, so the heart increases in its size by about 30 per cent during pregnancy,” she explained, adding that tissue composition and structure don’t just enlarge, but change.

“It literally changes into almost a new tissue. It’s completely different from what we see from other pathological conditions. If you parallel heart failure and pregnancy, as far as the heart valves are concerned, they both see the same thing.”

In heart failure, Wells said the valves often deteriorate and fail, requiring surgical removal and replacement. But there’s something about pregnancy that instead signals a physiological ad- aptation to handle the challenges of pregnancy.

“That’s really remarkable. It’s the first time we’ve shown sort of nonpathological adaptations of these tissues,” she said.

Wells said if they can understand the mechanisms driving this adaptation in the maternal heart, it may translate to developing treatments for conditions like heart failure or heart valve disease.

“If we had some way of convincing a heart valve in a patient say with heart failure … convince that heart valve that it’s in the heart of a pregnant animal or a pregnant human, it’s receiving some other signals other than just a mechanical load increase,” she said.

“If we can figure out what those mechanisms driving this amazing adaptive response are, it could develop into potentially a treatment. That’s my future work.” That work requires researchers with expertise in the areas of cell biology, molecular genetics, and others. Wells said her collaborators in cardiovascular research at Dalhousie include a broad range of scientists and clinicians all hoping to answer these questions.

“All of this adaptive response is obviously in pursuit of having afetus come to term successfully, and every time I present this at a conference people always ask what happens after birth? What happens to all this extra tissue?” she said.

“The answer is that we don’t know and nobody else does.”

As a first step to answering this question, Wells has a group of five first-year students col- lecting cattle hearts from animals that have never been pregnant and others that have experienced multiple pregnancies. Her students will compare the two groups, working on the hypothesis that tissues will be permanently enlarged and biomechanically altered in animals with multiple pregnancies.

“This is based on the hypothesis that these changes that happen during pregnancy do not fully reverse and the accumulation of those changes over multiple pregnancies can increase your risk for cardiovascular disease later in life,” Wells explained. “The epidemiology studies show that your risk for a cardiovascular event increases during pregnancy, it’s augmented with subsequent pregnancies, and your risk never returns to baseline.” Women have long been under-represented in medical research studies, with the bulk of medical research conducted mainly on male subjects. Wells said that’s why she applauds the relatively recent shift that has funding agencies and medical journals requesting or requiring researchers to address and sex or gender differences in their subjects. Her work highlights why this is important.

“It’s turning out that the maternal adaptation to pregnancy may hold a lot of answers into our understanding of how these tissues adapt, how they might fail, and maybe some possibilities of developing new treatment … You really need to study men and women in order to get a full picture, a complete picture of the system.”

“If you parallel heart failure and pregnancy, as far as the heart valves are concerned, they both see the same thing.” SARAH WELLS DALHOUSIE UNIVERSITY