Global profiling of the proteome and acetylome in mice with abdominal aortic aneurysms

Abstract

BackgroundAbdominal Aortic Aneurysm (AAA) is a life-threatening vascular condition characterized by a progressive dilation of the abdominal aorta and a high risk of rupture. Currently, no effective pharmacological therapies are available, and treatment relies mainly on surgical intervention. The lack of drug targets is largely due to limited understanding of the molecular mechanisms underlying AAA development. This study aims to identify potential therapeutic targets by performing comprehensive proteomic and acetylomic analyses in a mouse model of AAA. MethodsWe conducted global proteomic and acetylomic profiling on abdominal aortic tissues collected from an AAA mouse model. A total of 7,858 proteins and 1,790 acetylated proteins encompassing 4,581 acetylation sites were quantified. Bioinformatics analyses were performed to investigate the regulatory networks and biological pathways associated with these proteins and post-translational modifications. ResultsIntegrated analysis revealed that histone-related proteins were significantly enriched in pathways co-regulated by the proteome and acetylome. These pathways are influenced by histone acetyltransferases and deacetylases, implicating histone acetylation in AAA-related inflammatory and immune processes. Notably, the deacetylases Sirt2 and Sirt5 were identified as potential regulators of neutrophil extracellular trap (NET) formation through suppression of histone acetylation. ConclusionsThis study provides the first comprehensive proteomic and acetylomic dataset for abdominal aortic tissues in a mouse model of AAA, substantially expanding the mouse acetylation database. The results highlight the central role of histone modifications in immune dysregulation and inflammation, and propose Sirt2 and Sirt5 as candidate therapeutic targets that may inhibit NET formation and slow AAA progression. These findings suggest new avenues for drug development targeting the sirtuin family, although further experimental validation and cross-species studies are needed to confirm translational relevance. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=145 SRC="FIGDIR/small/657536v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@1c397a3org.highwire.dtl.DTLVardef@188180org.highwire.dtl.DTLVardef@de1a59org.highwire.dtl.DTLVardef@193e740_HPS_FORMAT_FIGEXP M_FIG C_FIG