CCL19 emerges as a regional signal in human abdominal aortic aneurysm through targeted proteomic and transcriptomic profiling of the aneurysmal wall and neck.
Abstract
BACKGROUND AND AIM: The molecular mechanisms underlying abdominal aortic aneurysm (AAA) progression remain incompletely understood and may vary across anatomically distinct regions of the diseased aorta. We hypothesised that the aneurysmal wall and aneurysm neck exhibit distinct molecular profiles, reflecting regional heterogeneity in AAA tissue. To this end, we characterized and compared targeted proteomic and transcriptomic profiles of these two anatomically distinct regions to identify molecular alterations associated with AAA pathology. METHODS: Paired aneurysmal wall and aneurysm neck tissues were obtained from 18 patients with AAA. Inflammatory proteins were quantified using the Olink Target 48 cytokine panel, with 45 proteins retained for analysis after quality-control filtering. Directional RNA sequencing was subsequently performed on matched tissue samples to characterize the expression of genes corresponding to the proteins included in the proteomic analysis and to assess concordance between transcriptomic and proteomic differences. RESULTS: Proteomic analysis identified three differentially expressed proteins (IL6, IL15, CCL19) between aneurysmal wall and neck. Transcriptomic analysis of the corresponding genes identified three differentially expressed transcripts (CCL19, CCL11, LTA). CCL19 was consistently elevated at both the protein and transcript levels in aneurysmal wall, whereas the remaining molecular alterations were specific to either the proteomic or transcriptomic analysis. CONCLUSIONS: Aneurysm wall and neck tissues showed largely similar inflammatory molecular profiles, with only a limited number of regional differences identified either on the protein or transcript level. CCL19 being the only concordant signal in both proteomic and transcriptomic analysis.
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