Atherosclerotic Fibrous Plaques in Women Present ECM Remodeling Linked to TGF-β

Tim R. Sakkers, Eloi Mili, Hanna Winter, Daniek Kapteijn, R. Noah Perry, Nicolas Barbera, Kelsey Watts, Inês R. Dias, Denitsa Meteva, Marian Wesseling, Barend M. Mol, Gert J. de Borst, Dominique P.V. de Kleijn, Sander W. van der Laan, Mete Civelek, Stephen J. White, Lars Maegdefessel, Manuel Mayr, Gerard Pasterkamp, Michal Mokry, Ernest Diez Benavente, and Hester M. den Ruijter. Circulation Research Volume 138, Issue 5, 27 February 2026; Page e327624 .

Cardiovascular disease presents differently in women and men, yet the molecular mechanisms underlying these differences remain poorly understood. In this study, researchers performed comprehensive multiomics analyses of human carotid atherosclerotic plaques to investigate sex-specific differences in plaque biology. They found that fibrous plaques from women exhibited enhanced extracellular matrix (ECM) remodeling, increased transforming growth factor-beta (TGF-β) signaling, and greater evidence of endothelial-to-mesenchymal transition (EndMT) compared with plaques from men.

These findings suggest that TGF-β-driven ECM remodeling contributes to the distinct structural characteristics of women’s atherosclerotic plaques, which are more often associated with plaque erosion rather than plaque rupture. By identifying sex-specific molecular pathways involved in plaque development and stability, this study provides new insights into the biological basis of cardiovascular disease in women and highlights potential targets for personalized therapeutic strategies.