Understanding women's biology could reshape the future of heart disease research
Women have long been underrepresented in cardiovascular research. Even today, many of the models used to understand the heart's arteries only partly account for the biological differences between women and men. A new ERC-funded research project at Aarhus University aims to help close that knowledge gap.
When a woman develops heart disease, it is not always the same disease - or driven by the same biological mechanisms - as in men.
Some cardiovascular diseases occur almost exclusively in women. Others present with different symptoms, develop differently or are associated with different risk factors.
This is no coincidence. Part of the explanation is that women have historically been underrepresented in cardiovascular research. But according to Monika Colombo, Associate Professor at Aarhus University, that is only half the story.
"Fortunately, we have become much better at including women in clinical research. But we are still not very good at incorporating the biology that makes women and men different into the models we use to understand cardiovascular disease. That is the fundamental knowledge we are still missing," she says.
Colombo now hopes to address that challenge through DISSEX, a research project awarded a prestigeous €1.5 million ERC Starting Grant under the European Union's Horizon Europe programme.
The project will investigate how hormones, stress and genetic factors influence women's coronary arteries and develop new models to explain why certain cardiovascular diseases affect women differently from men.
Why does an artery suddenly become vulnerable?
Researchers already understand a great deal about how blood flows through the coronary arteries and the mechanical forces acting on the vessel wall.
What they understand far less well is how the body's own biological signals influence the cells that make up those blood vessels.
How do hormonal changes affect the strength of an artery throughout life? What role does physical and psychological stress play? And how do genetic factors interact with the mechanical forces that arteries experience every second of every day?
Current scientific models can only partly answer those questions.
Through DISSEX, Colombo's team will bridge biology and biomechanics. By combining laboratory experiments, advanced medical imaging and computational modelling, the researchers will investigate how biological signals gradually alter the properties of blood vessels—and how those changes may eventually make an artery vulnerable to rupture.
"Today we can measure hormones and we can study the shape of blood vessels. What we still lack is an understanding of how the body's biology changes the cells within the vessel wall over time. That is the missing connection we are trying to uncover," says Colombo.
A disease that exposes a wider knowledge gap
The project focuses on Spontaneous Coronary Artery Dissection (SCAD), a condition in which a spontaneous tear develops within the wall of a coronary artery.
SCAD predominantly affects women, many of whom have none of the traditional risk factors associated with cardiovascular disease.
Simon Winter sees these patients in his clinical work. He is a consultant cardiologist at the Department of Cardiology at Gødstrup Regional Hospital and a clinical professor at Aarhus University, and serves as an advisor to the project.
"We see younger women coming in with what initially looks like a heart attack, but the underlying cause is not the usual build-up of plaque in the arteries. Instead, a tear develops in the artery wall, which can obstruct the flow of blood. It is a serious condition that can strike relatively early in life, and it can also take a considerable psychological toll on patients," he says.
This is precisely why SCAD challenges our current understanding of cardiovascular disease.
If clinicians are to become better at identifying who is at risk, understanding the mechanics of blood vessels alone is not enough. They also need to understand how hormones, stress and genetic factors shape the biology of the artery wall throughout a person's life.
To achieve this, the researchers will study living human coronary artery tissue and combine those findings with patient data and advanced computational models. Their goal is to uncover the biological mechanisms that gradually make an artery more susceptible to dissection.
"This is an area where we still lack fundamental knowledge. We need to understand why the condition occurs. Are some artery walls particularly vulnerable? Do hormones play a role? Or is it the result of several factors interacting? If we can identify markers and gain a better understanding of how the disease develops, we may also become better at knowing what to look out for in our patients," says Simon Winter.
From fundamental biology to more precise cardiovascular medicine
In the longer term, the researchers aim to develop personalised rupture-risk maps of the coronary arteries.
By integrating knowledge about hormones, genetics and biomechanics, they hope to identify patients at increased risk earlier and provide clinicians with better tools for diagnosis, monitoring and treatment planning.
For Colombo, however, the project's significance extends well beyond a single disease.
She hopes DISSEX will help reshape how researchers investigate women's cardiovascular health more broadly.
"If we want precision medicine, we also need models that reflect the biological diversity of patients. Women's cardiovascular physiology should not simply be regarded as a variation of a male standard. It deserves to be understood on its own biological terms," she says.
Aarhus University is home to several major initiatives focusing on women’s health. Here are five examples:
- The research project Women’s Health and Well-being is conducting Denmark’s largest-ever study of women’s health and well-being, including a survey of 300,000 women.
- PREG-AID investigates how medicines used to treat autoimmune diseases affect both mother and child during pregnancy.
- The FEMaLe project uses artificial intelligence and health data to improve the detection and treatment of endometriosis. The project has helped raise awareness of the disease in both Denmark and the EU.
- The BIOSFER project investigates the reasons behind declining fertility and explores how biological, social and psychological factors contribute.
- The Women’s Health Network brings together researchers and other stakeholders to strengthen research into women’s health..
Contact
Associate Professor Monika Colombo
Department of Mechnical and Production Engineering, Aarhus Universitey
Mail: mc@mpe.au.dk
Tel: +4522189869
Jesper Bruun
Journalist, Aarhus University
Mail: bruun@au.dk
Tel.: +4542404140