The study investigates the role of the deubiquitinase OTUB1 in vascular smooth muscle cells (VSMCs) within the context of atherosclerosis, a disease characterized by lipid accumulation and plaque formation in arteries. Atherosclerosis is a major cause of cardiovascular and cerebrovascular diseases, with VSMCs playing a significant role in its development. The research explores the potential of targeting OTUB1 to modulate the phenotype switch of VSMCs, which is considered a critical pathological process in atherosclerosis.
Ubiquitylation, a post-translational modification, has been implicated in the regulation of VSMC phenotype switch. Deubiquitinases, such as OTUB1, can remove ubiquitin chains from substrates, protecting proteins from degradation. The study hypothesizes that OTUB1 may influence the pathophysiology of VSMCs during atherosclerosis by modulating the stability of proteins like PDGFRβ, a key player in cell proliferation and migration.
To test this hypothesis, researchers constructed an atherosclerosis mouse model and used human aortic smooth muscle cells (HASMCs) to investigate the effects of OTUB1 depletion on phenotype changes and molecular mechanisms. The findings indicate that knocking down OTUB1 ameliorates plaque progression and stabilizes atherosclerotic plaques. Mechanistic insights reveal that OTUB1 increases the stability of PDGFRβ by removing K48-linked ubiquitylation, thus inhibiting the phenotype switch of VSMCs.
The study further demonstrates that .