ERC Grant Targets Sex-Based Biology Behind Women’s Heart Disease

When a woman develops heart disease, it is not always the same disease—or driven by the same biological mechanisms—as it is in men. Some cardiovascular conditions occur almost exclusively in women, while others present with different symptoms, progress differently, or are linked to different risk factors. A new research project at Aarhus University in Denmark now aims to address one of the fundamental reasons this knowledge gap persists: the biology that distinguishes female from male cardiovascular systems remains poorly represented in the scientific models used to study the heart’s arteries.

The project, known as DISSEX, has been awarded a €1.5 million ERC Starting Grant under the European Union’s Horizon Europe programme. It is led by Monika Colombo, Associate Professor at Aarhus University, who argues that the underrepresentation of women in cardiovascular research is only half of the problem. Clinical research has become considerably better at including women as participants, she notes, but the field still struggles to incorporate sex-based biological differences into the models used to understand cardiovascular disease. It is this missing fundamental knowledge that DISSEX is designed to address.

The scientific premise of the project rests on a well-recognised asymmetry in cardiovascular research. Researchers already understand a great deal about how blood flows through the coronary arteries and about 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 across a woman’s life affect the strength of an artery? What role does physical and psychological stress play? And how do genetic factors interact with the mechanical forces that arteries experience continuously? Current scientific models can only partly answer these questions.

DISSEX will attempt to 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. Colombo describes the missing link in concrete terms: today it is possible to measure hormones and to study the shape of blood vessels, but science still lacks an understanding of how the body’s biology changes the cells within the vessel wall over time. Uncovering that connection between biological signals and cellular change is the central aim of the project.

The clinical focus of DISSEX is Spontaneous Coronary Artery Dissection, or 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. This makes the condition a particularly striking example of why understanding the mechanics of blood vessels alone is insufficient. If clinicians are to become better at identifying who is at risk, they also need to understand how hormones, stress and genetic factors shape the biology of the artery wall throughout a person’s life.

Simon Winter, a consultant cardiologist at the Department of Cardiology at Gødstrup Regional Hospital and a clinical professor at Aarhus University, serves as an advisor to the project and sees these patients in his clinical work. He describes younger women arriving with what initially looks like a heart attack, but with a fundamentally different underlying cause: rather than the usual build-up of plaque in the arteries, a tear develops in the artery wall that can obstruct the flow of blood. He characterises SCAD as a serious condition that can strike relatively early in life and that can also take a considerable psychological toll on patients.

Winter emphasises that SCAD exposes a wider gap in fundamental knowledge. Researchers still need to understand why the condition occurs at all. Are some artery walls particularly vulnerable? Do hormones play a role? Or is the disease the result of several factors interacting? If markers can be identified and a better understanding gained of how the disease develops, clinicians may also become better at knowing what to look out for in their patients. These are precisely the questions DISSEX is structured to investigate.

Methodologically, the project will study living human coronary artery tissue and combine those findings with patient data and advanced computational models. The goal is to uncover the biological mechanisms that gradually make an artery more susceptible to dissection. By integrating knowledge about hormones, genetics and biomechanics, the researchers hope in the longer term to develop personalised rupture-risk maps of the coronary arteries. Such maps could, in principle, help identify patients at increased risk earlier and provide clinicians with better tools for diagnosis, monitoring and treatment planning. These are the project’s stated aims; the models and their clinical utility remain to be demonstrated through the research itself.

For Colombo, however, the significance of the project extends well beyond a single disease. She hopes DISSEX will help reshape how researchers investigate women’s cardiovascular health more broadly. In her view, precision medicine requires models that reflect the biological diversity of patients, and women’s cardiovascular physiology should not simply be regarded as a variation of a male standard. Instead, she argues, it deserves to be understood on its own biological terms—a reframing that could influence how future studies of the heart and arteries are designed across the field.

The grant also situates Aarhus University within a broader institutional effort on women’s health. The university hosts several major initiatives in this area, including the research project Women’s Health and Well-being, which is conducting Denmark’s largest-ever study of women’s health and well-being through a survey of 300,000 women. Other examples include PREG-AID, which investigates how medicines used to treat autoimmune diseases affect both mother and child during pregnancy; the FEMaLe project, which uses artificial intelligence and health data to improve the detection and treatment of endometriosis and has helped raise awareness of the disease in both Denmark and the EU; the BIOSFER project, which investigates the reasons behind declining fertility and explores how biological, social and psychological factors contribute; and the Women’s Health Network, which brings together researchers and other stakeholders to strengthen research into women’s health. Within this ecosystem, DISSEX adds a distinct biomechanical and biological dimension, targeting the mechanisms that make women’s coronary arteries behave differently from men’s—and, ultimately, aiming to close a knowledge gap that has shaped cardiovascular medicine for decades.

Subject of Research: Sex-based biological differences in coronary artery disease and the ERC-funded DISSEX project on women's cardiovascular health at Aarhus University

Article Title: Understanding women's biology could reshape the future of heart disease research

Article References: Understanding women's biology could reshape the future of heart disease research. Original publication (Bibliographic details unavailable.)

Image Credits: AI Generated

DOI: Not provided

Keywords: cardiovascular disease, women's health, SCAD, coronary artery dissection, ERC Starting Grant, Aarhus University, hormones, biomechanics, computational modelling, precision medicine, sex differences, artery rupture risk