Smooth muscle cell-related transcription factors have been associated with coronary artery disease in large genome-wide association studies, increasing their translational value for therapeutic investigations. Our study shows for the first time that FOXC1 is a major transcriptional regulator in vascular injury and atherosclerotic lesions, causally implicated in the disease. Functionally, our data suggest that FOXC1 modulates smooth muscle cell activation vs quiescence by regulating key pathways involved in cell adhesion, cell cycle progression, and actin cytoskeleton organization. Further investigations should focus on elucidating the mechanistic basis of these regulatory effects and assessing whether this axis could be pharmacologically targeted to promote lesion stability.
Rykaczewska et al. (Thu,) studied this question.