Arterial Health and Disease in Women

Research Context (Why we do research)

Our strength and originality reside in integrating the full spectrum of INSERM missions encompassing basic, translational, and preclinical research. Our research goes from gene discovery, in the context of rare and common diseases, to molecular and cellular translation, and ultimately, patients-driven clinical investigation.

Over the past decades, advances in cardiovascular medicine have greatly improved survival and outcomes—but not equally for everyone. Women have benefited less than men from these improvements, particularly in conditions linked to hypertension and its complications, such as myocardial infarction and strokes.

Some cardiovascular diseases that predominantly affect women remain underdiagnosed and poorly understood. Among these are spontaneous coronary artery dissection (SCAD) and fibromuscular dysplasia (FMD). SCAD causes a heart attack when a tear or hematoma within the wall of a coronary artery, blocking blood flow. Remarkably, about 90% of SCAD cases occur in women, typically in early to middle adulthood. Around half of these women also show signs of FMD—abnormal narrowing or bulging (stenosis and aneurysms) in other arteries.

FMD itself is often discovered late, usually after a complication such as high blood pressure, stroke, or SCAD. Unlike atherosclerosis, SCAD and FMD are not caused by plaque build-up or inflammation, and their biological mechanisms remain largely unknown. Progress has been slowed by the lack of large-scale studies and suitable animal models.

Interestingly, men and women also show different patterns of vascular ageing. Women are more likely to develop “early vascular ageing,” meaning that their arteries become stiff earlier in life. This contributes to a higher burden of cardiovascular risk in women, beyond traditional factors, and highlights the urgent need for sex-specific prevention and treatment strategies.

Our Research program (What is our work?)

To address this gap, our team has built a research program on genetics-driven research into SCAD and FMD, and on improving imaging-based biomarkers related to vascular aging. We are beginning to uncover the biological roots of these female-predominant cardiovascular diseases to pave the way for new diagnostic tools, preventive strategies, and targeted therapies tailored to women’s cardiovascular health.

1. Genetics and Genomics of SCAD and Related Arteriopathies – Contact: N Bouatia-Naji

We investigate the genetic and genomic bases of spontaneous coronary artery dissection (SCAD), fibromuscular dysplasia (FMD), mitral valve prolapse, and hypermobile Ehlers–Danlos syndrome. Using high-throughput genotyping and sequencing, we analyze large patient cohorts and controls through genome-wide association studies and advanced statistical genetics approaches. We integrate data from our own cohorts with large public resources to conduct multi-trait analyses relevant to these vascular and connective tissue diseases. Our research also focuses on omics integration using machine learning, polygenic risk scoring, and multi-ancestry genetic studies to better capture the global genetic architecture of these disorders.

2. Improving Cardiovascular Risk Stratification and Treatment in Women – Contact: RM Bruno

This research line examines the genetic and vascular determinants of early and supernormal vascular ageing in both sexes, with a special focus on women. By linking genetic factors, blood pressure regulation, and arterial stiffness, we aim to identify novel mechanisms and biomarkers of cardiovascular risk. Our team designs and conducts clinical studies testing personalized treatment strategies based on improved risk reclassification. We also develop and validate innovative, user-friendly devices for vascular ageing assessment, suitable for large population studies, primary care, and even self-monitoring, to promote precision prevention in cardiovascular health.

3. Molecular and Functional Translation of SCAD and FMD Genetic Loci- Contact : N Bouatia-Naji, A Georges

We explore the molecular mechanisms underlying genetic susceptibility to SCAD and FMD, emphasizing the key role of vascular smooth muscle cells (SMCs). Using advanced CRISPR-based systems and SMCs derived from human induced pluripotent stem cells (iPSCs), we perform functional genomic experiments enabling targeted gene activation. Our work aims to map the regulatory networks involved in SCAD and FMD, including their modulation by sex hormones. Through systematic variant screening, gene function analysis, and spatial gene expression profiling in human arteries, we seek to define the molecular signatures driving arterial remodeling and disease expression.