Global Analysis of the Lysine Acetylome in Macrophages from Salt-sensitive Hypertensive Rats

Research indicates that patients with salt-sensitive (SS) hypertension experience higher morbidity and target organ damage than in patients with non-SS hypertension. Dysregulated macrophage activation has been implicated in SS hypertension development, with lysine acetylation playing a role in modulating macrophage function. However, the role of macrophage acetylation patterns in SS hypertension remains unclear. This study aimed to investigate how acetylation regulates macrophage function and its role in the pathogenesis of SS hypertension. We employed quantitative acetylation proteomics to characterize the acetylome of bone marrow-derived macrophages in Dahl SS hypertensive rats fed either a high-salt or a low-salt diet. We identified 94 hyperacetylated and 49 hypoacetylated sites on 79 and 45 proteins, respectively, in the high-salt group. Notably, acetylation levels increased at lysine 20 (K20) and K46 on histone H2B, at K56 on H3, and at K77 and K79 on H4c2. We also identified conserved acetylation motifs, analyzed their Gene Ontology terms and pathways, and explored the protein-protein interactions of these differentially acetylated proteins using bioinformatics analyses. Finally, we validated the altered acetylation of H2, H3, H4, and several metabolic proteins using immunoprecipitation and western blotting. Overall, these findings offer insights into the role of lysine acetylation in macrophages from SS hypertensive rats, revealing potential therapeutic targets.