Atherosclerosis is a chronic inflammatory cardiovascular disease in which lipid-driven vascular injury, immune activation, and mitochondrial dysfunction contribute to plaque development and progression. It is discussed here as a disease context for ubiquitin specific proteases, with recent work indicating that USPs have dual and context-specific roles in atherosclerosis progression, including usp20-linked effects. The literature also highlights mitochondrial dysfunction as a key pathological feature and a therapeutic focus, especially in strategies aimed at mitochondrial-targeted delivery systems. In cell models, ox ldl-treated macrophages are used to mimic atherosclerosis-relevant inflammatory responses. Curcumin has anti-atherosclerotic potential by inhibiting the P2X7R-mediated inflammatory pathway and reducing TGF-β, NOX1, and MMP-3 expression. Overall, these findings support atherosclerosis as a multifactorial disease with emerging therapeutic avenues spanning proteostasis, inflammation, and organelle-targeted intervention.
Ubiquitin-protease and proteostasis
- A 2026 European Journal of Pharmacology review (PMID:41747799) framed atherosclerosis as a cardiovascular disease targeted by ubiquitin-specific protease-based therapeutic strategies. (PMID:41747799)
- Recent studies emphasize the key functions of ubiquitin specific proteases in atherosclerosis pathogenesis, suggesting protease-directed intervention beyond conventional approaches. (PMID:41747799)
- usp20 was highlighted as having dual and context-specific roles in atherosclerosis progression, indicating that its effects may vary by disease stage or cellular context. (PMID:41747799)
Mitochondrial dysfunction
- A 2026 Drug Delivery review (PMID:41668545) identified atherosclerosis as a chronic inflammatory disease associated with mitochondrial dysfunction. (PMID:41668545)
- The same review focused on applications of mitochondrial-targeted delivery systems, underscoring mitochondria as a therapeutic entry point in atherosclerosis. (PMID:41668545)
- Mitochondrial dysfunction was presented as a mechanistic contributor to disease progression rather than a secondary feature. (PMID:41668545)
Inflammation and macrophage models
- ox ldl-treated macrophages were used as an atherosclerosis-relevant model to study inflammatory signaling. (PMID:42012656)
- A 2026 Naunyn-Schmiedeberg’s Archives of Pharmacology study (PMID:42012656) showed that curcumin inhibits the P2X7R-mediated inflammatory pathway in this model. (PMID:42012656)
- Curcumin also reduced TGF-β, NOX1, and MMP-3 expression, supporting an anti-inflammatory and anti-remodeling effect. (PMID:42012656)
- These findings support curcumin as a candidate for prevention and treatment of atherosclerosis. (PMID:42012656)