Inverse association between the extracellular matrix protein Tenascin-X and concurrent abdominal aortic calcification in patients with primary aldosteronism

Background Patients diagnosed with primary aldosteronism (PA) are at significantly increased risk of abdominal aortic calcification (AAC) and subsequent cardiovascular complications. Notably, abdominal aortic calcification is independently associated with adverse cardiovascular outcomes. However, to date, no serum proteomic profiling has been specially carried out in PA patients complicated with AAC, leaving an unaddressed research gap. This study was designed to identify serum differentially expressed proteins (DEPs) via DIA-based untargeted proteomics. Methods In this translational research project, data-independent acquisition (DIA) mass spectrometry was utilized to contrast serum proteomic landscapes from two PA subgroups: patients presenting with AAC and those without the calcification lesion. GO and KEGG functional enrichment analyses were conducted to decode biological functions of screened DEPs. Tenascin-X (TNX), an extracellular matrix molecule encoded by the TNXB gene, was selected as the core candidate and validated via aldosterone-exposed vascular smooth muscle cells (VSMCs) as well as aldosterone-intervened mice. Results In total, 38 DEPs were distinguished across the two patient cohorts, comprising 6 upregulated proteins and 32 proteins with lowered expression levels. Gene Ontology results illustrated these molecules predominantly reside within extracellular regions and take part in cellular adhesion and immune regulatory activities. KEGG pathway enrichment further highlighted prominent enrichment within the extracellular matrix receptor interaction cascade. Markedly suppressed TNX expression was detected in aldosterone-treated VSMCs ( P < 0.001). In mouse aortic specimens, merely a marginal declining tendency of TNX was observed, which failed to reach statistical significance ( P = 0.054). Conclusion This proteomic study analyzes serum protein profiles in primary aldosteronism patients with and without abdominal aortic calcification, and identifies reduced serum TNX expression in PA patients complicated by abdominal aortic calcification. Further cellular experiments and aldosterone-intervened mouse studies revealed downregulation or a downward trend of key candidate molecule TNX, providing partial preliminary experimental support for the proteomic-identified candidate TNX. This study offers new research ideas for subsequent mechanistic investigations into abdominal aortic calcification in patients with primary aldosteronism.