MYH9 Gene May Explain Heart Artery Plaques in Women

A gene called MYH9 may help explain why women are more likely than men to develop a specific type of artery plaque linked to heart disease, according to a study published in Circulation Research. Researchers at UCLA Health found that MYH9 plays a key role in forming fibrous plaques, which are more stable than other types but can still lead to heart attacks through erosion.

Heart disease remains the leading cause of death for women globally, yet it is often overlooked or misdiagnosed. Symptoms and imaging may not match what doctors typically see in men, complicating treatment. Fibrous plaques, which are thicker and less likely to rupture, are more common in women, particularly those under 50, but the biological reasons were unclear until now.

The study analyzed vascular smooth muscle cells from over 150 human donors, including 119 men and 32 women. They identified female-specific gene networks tied to inflammation, cell structure, and vascular changes. These networks appeared to influence how plaques form and stabilize in women’s arteries.

MYH9 was found to be more active in areas of plaque that form fibrous caps—the protective layers covering plaques. Higher levels of the gene correlated with plaques containing more smooth muscle cells and less fat, a hallmark of fibrous plaques. This suggests the gene may shape plaque structure in a sex-specific way.

Dr. Mete Civelek, a lead researcher on the study, said the team used advanced computational methods to compare gene activity between men and women. They also analyzed large datasets from the Netherlands and Sweden, reinforcing the link between MYH9 and fibrous plaque traits. “The differences were clearer when we looked at gene networks, not individual genes,” he said.

While the findings won’t change immediate patient care, they offer new insights into how sex differences affect heart disease biology. Understanding these mechanisms could eventually lead to more personalized risk predictions and treatments that account for gender-specific factors.

The next steps include exploring how MYH9 influences plaque biology differently in women and men. Researchers are also collaborating with Dr. Karen Reue to investigate if sex hormones or chromosomes drive variations in MYH9 activity. These studies may uncover new therapeutic targets for cardiovascular disease.

The research, led by UCLA and published in Circulation Research (DOI: 10.1161/circresaha.125.326941), highlights the importance of considering sex differences in cardiovascular research. It adds to a growing body of work showing how genetic and biological factors shape disease risk in distinct ways for men and women.