SIRT7 regulates smooth muscle phenotypic switching by deacetylating SRF to repress abdominal aortic aneurysm formation

Mechanistically, SIRT7-mediated deacetylation of serum response factor (SRF) at K154 maintained SRF transcriptional activity, suppressed its nuclear-to-cytoplasmic translocation and ubiquitin-dependent degradation, and preserved the VSMC contractile phenotype. Pathologically, SIRT7 deficiency increased SRF acetylation, accelerated its protein degradation, and exacerbated VSMC phenotypic switching, thereby promoting AAA formation.

Pharmacological activation of SIRT7 using nicotinamide mononucleotide (NMN), a precursor of NAD+ biosynthesis, inhibited VSMC phenotypic switching and therapeutically attenuated aortic dilation. Collectively, our findings reveal the intricate mechanisms underlying SIRT7-mediated SRF K154 deacetylation to inhibit AAA progression. Importantly, NMN supplementation may be an effective therapeutic strategy for AAA.