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.