BAHCC1 Drives Smooth Muscle Plasticity and Neointima via Epigenetic Repression

Runze Tang, Yitao Huang, Takuro Shirasu, Jing Li, Amy Webb, Kaiyuan Zheng, Chengli Shen, Yiran Guo, Gaelle Auguste, Patrick Hart, Maria Murach, Xinyu Zhou, Jianjie Ma, K Craig Kent, Gang Greg Wang, Jie Yang, Clint L Miller, Kathleen Ann Martin, Lian-Wang Guo

We recently published this collaborative work in Circulation Research on October 29, 2026.

Abstract:
Vascular smooth muscle cell phenotypic plasticity contributes to neointimal hyperplasia, restenosis, and atherosclerosis, yet the epigenetic mechanisms governing these processes remain incompletely understood. Here, we identify BAHCC1, a reader of the repressive histone modification H3K27me3, as a key regulator of pathological vascular remodeling. BAHCC1 is upregulated in diseased human arteries and experimental models of vascular injury. Genetic deletion, silencing, or disruption of its H3K27me3-binding activity attenuates neointimal hyperplasia. Integrated transcriptomic and epigenomic analyses reveal that BAHCC1 promotes smooth muscle cell dedifferentiation by repressing LMO7 through H3K27me3 recognition and recruitment of transcriptional corepressors, including SAP30 and RBBP4/7. These findings establish BAHCC1 as an epigenetic driver of vascular smooth muscle cell plasticity and identify the BAHCC1 pathway as a potential therapeutic target for vascular diseases.