For decades, the people at higher risk of suffering from cardiovascular diseases were older men, who smoked, and led a stressful lifestyle. However, over time, women have adopted similar lifestyles and today, a woman is more likely to die from a heart attack or a stroke than from breast cancer. According to Bouatia-Naji, principal investigator of the ROSALIND project, cardiovascular diseases in women are often misdiagnosed as anxiety or fatigue because medical staff underestimate their risk.

Additionally, symptoms of cardiovascular disease are sometimes different in women and men. In some cases women can seem in good health, exercising regularly, maintaining a balanced diet, with normal lipid blood levels, without being overweight and in their 40s or 50s. These are the cases where the diagnosis becomes even more difficult.

Studying two atypical diseases in women

The ROSALID projects aims to uncover the genetic and molecular causes of two cardiovascular diseases that belong to this atypical category: fibromuscular dysplasia and spontaneous coronary artery dissection. Eighty to ninety percent of patients who develop these diseases are women who don’t present the usual clinical symptoms associated with cardiovascular disease.

In both diseases, the underlying cause is not the typical obstruction of arteries caused by the accumulation of fats and chronic inflammation that develop over time. Instead, arteries in these patients lose their integrity and become narrower because the muscles around the arteries are weakened, cells are disorganised and this may lead to tears. This results in a diminished blood flow and leads to high blood pressure, stroke or heart attack.

An angio-coronary image from a patient with spontaneous coronary artery dissection.
The dark colour indicates clotted blood (hematoma), causing the blockage of the artery and resulting in a heart attack

According to clinical observations, these two diseases may be triggered by gender-related factors such as hormonal cycles and pregnancy but we do not yet understand how this happens. Additionally, women whose female relatives had a stroke have a higher risk of suffering from a stroke themselves. This suggests that inheritance may interact with gender-related factors to further amplify the higher prevalence of these diseases in women.

A new approach: combining genetic and molecular studies

Understanding the underlying biological and genetic causes of human disease is crucial for the development of specific treatments. For this purpose, ROSALIND is conducting a combination of genetic and molecular studies.

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As part of the genetic studies, researchers are comparing genomes in groups of patients that have the disease with healthy control groups. This way, researchers hope to identify genetic differences and defects that cause these conditions.

At the same time, they are studying the organisation of the DNA in the cells that form the musculature of the diseased arteries. This allows them to better target the genetic defects specifically involved in maintaining the alignment of artery cells.

According to Bouatia-Naji, the novelty of ROSALIND lies in this combination of the genetic and the molecular studies applied to the two diseases that have never before been studied from this perspective.

Through their research, Bouatia-Naji and her team have already demonstrated the existence of two genes that provide common genetic features between the two diseases, a promising finding that strongly supports her approach to the study.

The importance of curiosity-driven health research

According to Bouatia-Naji, the ERC grant gave her visibility in the academic world and allowed her to position herself among the global experts of cardiovascular genetics.

The main aim of my project is to understand the genetic basis and the first molecular regulation of genes involved in atypical cardiovascular diseases affecting mostly women. I want to study them because I want to know why these women are prone to have a cardiac event while they should not because they look healthy. It is definitely, curiosity-driven science.

‘I am very grateful to those who developed the ERC-funding scheme’, she says. ‘The main aim of my project is to understand the genetic basis and the first molecular regulation of genes involved in these atypical cardiovascular diseases. I want to study them because I am extremely curious to know why these women have a cardiac event while they should not because they look healthy. It is curiosity-driven science and this is becoming very rare and not supported by many national funding schemes. This funding gave me hope that it is still possible to get funding for frontier and basic health research, which is fundamental for designing new treatments in the future.’

When research comes out of the laboratory

Bouatia-Naji is also an avid promoter of her work outside of the lab. She often gives talks and participates in outreach activities – for example, she was chosen as the national contact for the Science Festival 2019, a nation-wide manifestation to promote science in France.

She finds it important to share her research with a lay audience, in an effort to make them aware about atypical cardiovascular diseases in women. ‘I appreciate when people, especially women, seem to learn that this is an important research field and are so surprised when they see it is under-studied in general and that I am contributing to bridging this gap in our current knowledge’, she says.

Biography

Nabila Bouatia-Naji is a molecular geneticist and an INSERM (French National Institute of Health and Medical Research) research director at the Paris cardiovascular research center, University of Paris, France. Her multidisciplinary team includes statistical geneticists, molecular biologists and clinicians who investigate the genetics and genomics of vascular disease predominant in women. She is an active advocate for more leadership opportunities for women in health science.