A new study has revealed important differences in how carotid artery narrowing, a major risk factor for stroke, affects men and women.
Published in Nature Cardiovascular Research, the study found that although men and women develop similar types of artery plaque, the small details within the cells are quite different—and those differences may affect stroke risk and treatment.
The carotid arteries are major blood vessels in the neck that supply blood to the brain. When these arteries become narrowed by a buildup of fatty substances called plaques, the risk of stroke increases.
According to the World Health Organization, strokes and heart attacks together account for about 85% of the 17.9 million deaths caused by cardiovascular diseases each year.
Katyayani Sukhavasi, a Ph.D. student in medicine at the University of Tartu and one of the authors of the study, explained that biological sex has a major effect on how carotid narrowing, also known as carotid stenosis, develops. It also affects the overall risk of heart and brain disease. These effects are influenced by age and changes such as menopause.
Generally, men tend to develop cardiovascular diseases earlier in life and are more likely to have plaques in their arteries that are rich in fat and prone to bleeding. Women, on the other hand, usually experience artery narrowing later in life.
Before menopause, female hormones may offer some protection. Women’s plaques are more likely to erode gradually, rather than suddenly rupture.
To better understand these differences, the researchers collected plaque samples from both men and women during surgery to remove blockages from their neck arteries. Then they used a powerful tool called single-cell RNA sequencing to look at individual cells from the plaques.
This method helps researchers see which genes are active in each cell, allowing them to learn more about what those cells are doing.
The analysis found that while the major cell types—like smooth muscle cells, immune cells (macrophages), and the inner lining cells of blood vessels (endothelial cells)—were mostly the same in both sexes, the smaller structures and functions inside those cells were different.
In plaques from women, there were more smooth muscle cells that can turn into bone-like tissue (osteogenic cells), more macrophages involved in controlling immune responses, and more endothelial cells that were transitioning into another type of cell called mesenchymal cells. This type of cell change may influence how plaques grow and break down.
In men’s plaques, there were more smooth muscle cells that resembled cartilage cells (chondrocyte-like cells), more macrophages involved in tissue remodeling, and more endothelial cells that were helping grow new blood vessels (angiogenesis). These features can make plaques more unstable and likely to cause problems like sudden bleeding or stroke.
The researchers believe that understanding these sex-specific differences could lead to better, more personalized treatments.
The study also showed that the genes active in these cells and the networks they form—called gene regulatory networks—were different between men and women. These differences may hold clues to why the disease behaves differently and how it could be treated more effectively for each sex.
Sukhavasi stressed the importance of treating biological sex as a key factor in medical research. By recognizing how men and women may develop different types of artery disease, doctors and scientists can improve the accuracy of diagnoses, predict stroke risk more reliably, and design treatments that work better for each individual.
In summary, this research highlights that while carotid artery narrowing is a serious risk for everyone, the way it develops and behaves in the body can differ significantly between men and women. Taking these differences into account could help save lives and improve care for people at risk of stroke.
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The research findings can be found in Nature Cardiovascular Research.
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