Myeloid BAF60a deficiency alters metabolic homeostasis and exacerbates atherosclerosis

Atherosclerosis, a leading health concern, stems from the dynamic involvement of immune cells in vascular plaques. Despite its significance, the interplay between chromatin remodeling and transcriptional regulation in plaque macrophages is understudied. We discovered the reduced expression of Baf60a, a component of the switch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complex, in macrophages from advanced plaques. Myeloid-specific Baf60a deletion compromised mitochondrial integrity and heightened adhesion, apoptosis, and plaque development. BAF60a preserves mitochondrial energy homeostasis under pro-atherogenic stimuli by retaining nuclear respiratory factor 1 (NRF1) accessibility at critical genes. Over expression of BAF60a rescued mitochondrial dysfunction in an NRF1-dependent manner. This study illuminates the BAF60a-NRF1 axis as a mitochondrial function modulator in atherosclerosis, proposing the rejuvenation of perturbed chromatin remodeling machinery as a potential therapeutic target.

Automated summary

This study reveals the role of BAF60a-NRF1 axis as a modulator of mitochondrial function in atherosclerosis. Macrophages in advanced plaques show reduced expression of Baf60a, leading to compromised mitochondrial integrity and increased adhesion, apoptosis, and plaque development. Over expression of BAF60a rescues mitochondrial dysfunction in an NRF1-dependent manner.