A new study published in Nature Cardiovascular Research found that while carotid artery narrowing can lead to stroke in both men and women, the symptoms and plaque characteristics often differ between the sexes. Even though the main types of cells in the plaques are similar, important differences exist in the smaller structures within those cells.
According to the World Health Organization, cardiovascular diseases cause 17.9 million deaths worldwide. Of these, heart attacks and strokes were responsible for 85%.
Katyayani Sukhavasi, a PhD student in Medicine at the University of Tartu and one of the study's authors, explained that biological sex has a significant influence on carotid stenosis, i.e., carotid artery narrowing, the development of atherosclerosis, and overall cardiovascular risk — factors that are further affected by age and menopause. “Men tend to develop cardiovascular diseases earlier and are more susceptible, often showing lipid-rich plaques and bleeding. In contrast, women—possibly due to protective effects of pre-menopausal hormones—typically develop carotid stenosis later, with plaque erosion being more common,” said Sukhavasi.
Consequently, understanding these sex-specific differences in carotid artery narrowing is crucial. This study used single-cell RNA sequencing to analyze cells from carotid plaques collected during surgery to remove blockages from the neck arteries in both women and men. Advanced bioinformatic analysis of the dataset revealed significant sex-biased differences in the subcellular composition of carotid plaques, despite minimal variations in major cell types such as smooth muscle cells, macrophages, and endothelial cells.
Sukhavasi explained that specifically, females had more osteogenic smooth muscle cells, macrophages that help regulate the immune response, and endothelial cells that were changing into mesenchymal cells. Males, on the other hand, had more chondrocyte-like smooth muscle cells, macrophages involved in tissue remodeling, and angiogenic endothelial cells that promote the formation of new blood vessels.
The study “Single cell RNA sequencing reveals sex differences in the subcellular composition and associated gene-regulatory network activity of human carotid plaques" conducted by Katyayani Sukhavasi, Heli Järve, Arno Ruusalepp, and Johan Björkgren highlights that understanding sex-specific molecular mechanisms and gene regulatory networks in atherosclerotic plaques can help identify potential therapeutic targets for each sex.
Sukhavasi emphasized that investigating biological sex as a critical variable in atherosclerosis is essential for gaining a more comprehensive understanding of the disease, improving risk prediction, ensuring more accurate diagnosis, and developing personalized and effective prevention and treatment strategies for both men and women.
Nature Cardiovascular Research
Experimental study
Human tissue samples
Single-cell RNA sequencing reveals sex differences in the subcellular composition and associated gene-regulatory network activity of human carotid plaques
10-Apr-2025
J.L.M.B. and A.R. are shareholders of Clinical Gene Networks AB (CGN) that has an invested interest in STARNET. C.L.M. has received funding from AstraZeneca for an unrelated project. All other authors declare no competing interests.