Researchers at UCLA Health have pinpointed the culprit behind a crucial difference in how women and men develop heart disease: a gene called MYH9 that shapes the structure of arterial plaques in distinctly female patterns.
The discovery, published in Circulation Research, matters because heart disease remains the leading killer of women globally—claiming more lives than all forms of cancer combined—yet remains frequently overlooked or misdiagnosed because women's symptoms and imaging don't match the textbook male presentation. For decades, scientists knew that women, particularly those under 50, tend to develop different types of arterial plaques than men, but the biological machinery driving these differences stayed hidden.
Dr. Mete Civelek, a professor of human genetics at UCLA's David Geffen School of Medicine and the study's corresponding author, led an international team through painstaking detective work. They analyzed gene activity in vascular smooth muscle cells—the cells that build and maintain blood vessel structure—from 151 human donors: 119 males and 32 females. The researchers isolated cells directly from donated hearts and used advanced computational methods to compare how genes work together in networks, a technique that proved far more revealing than studying individual genes alone.
What they found was striking. Two female-biased "gene programs" emerged in the vascular smooth muscle cells, with MYH9 standing out as especially significant. When MYH9 ran at higher levels, plaques developed with more smooth muscle cells and less fat content—the defining characteristics of fibrous plaques. These smoother, scar-like plaques are generally more stable than the unstable plaques prone to sudden rupture, but they still cause heart attacks and other cardiac emergencies through a slower process called plaque erosion. MYH9 proved especially active in the fibrous cap, the protective layer that covers the plaque itself.
The implications are cellular and intimate. The gene appears to influence how vascular cells respond to their physical environment—the mechanical stress flowing blood exerts on vessel walls—and to biological signals like hormones. This responsiveness seems to sculpt plaque structure in sex-specific ways, explaining why women's hearts build plaques differently.
To verify their findings, Civelek's team consulted large human cohort studies from the Netherlands and Sweden that contained actual plaque samples, a crucial confirmation step. "What was especially exciting was that the differences were much clearer when we looked at how genes work together in networks, rather than looking at one gene at a time," Civelek explained. "It was also encouraging that several different kinds of data all pointed to the same gene, MYH9, which makes us more confident that it is biologically important."
The work won't transform clinical care overnight. But it cracks open the black box of sex-specific cardiovascular biology, creating a foundation for more targeted medicine. As Civelek noted, understanding these mechanisms "will help to develop more personalized ways to predict risk and design treatments that take sex differences into account." For women whose heart disease has long been treated through a male-centered lens, this shift toward biology-based precision represents genuine hope for better diagnosis and care.