Global Profiling of the Proteome and Acetylome in Mice with Abdominal Aortic Aneurysms

Abdominal aortic aneurysm (AAA) is a fatal vascular disease with a high rupture risk, and current treatments rely mainly on surgery. Pharmacological therapies are limited due to an incomplete understanding of disease mechanisms. This study aimed to identify potential targets for pharmacological intervention in AAA using a mouse model, focusing on proteomic and acetylomic alterations in aortic tissues. We successfully established a mouse AAA model and performed global proteomic and acetylomic analyses, identifying 7858 quantifiable proteins and 1790 acetylated proteins with 4581 acetylation sites. Bioinformatics analyses revealed that histones were enriched in pathways co-regulated by the proteome and acetylome and were modulated by histone acetyltransferases and deacetylases. Sirt2 and Sirt5 were predicted to inhibit neutrophil extracellular trap (NET) formation by suppressing histone acetylation, thereby potentially attenuating the progression of AAA. This study proposes that Sirt2 and Sirt5 may inhibit neutrophil extracellular trap (NET) formation by suppressing histone acetylation, potentially slowing AAA progression. Sirt2 and Sirt5 may represent potential therapeutic targets, providing a foundation for exploring the effect of the sirtuin protein family on AAA treatment.