Cross-Omics Identification and Validation of PCSK9 as a Candidate Molecule Associated with Aortic Dissection and...

Background: Negative aortic remodeling after thoracic endovascular aortic repair (TEVAR) remains a major challenge in patients with type B aortic dissection (TBAD). This exploratory study aimed to integrate human aortic tissue transcriptomic data with serum proteomic profiles from a remodeling-stratified TEVAR cohort to prioritize candidate molecules associated with TBAD and negative aortic remodeling. Methods: Public human aortic tissue transcriptomic data from GSE190635 were analyzed to identify differentially expressed genes between aortic dissection and control aortic tissues. Serum tandem mass tag (TMT)-based untargeted proteomic profiling was performed in a remodeling-stratified TEVAR cohort, including patients with negative remodeling and those with stable or positive remodeling. Cross-omics integration was conducted by intersecting differentially expressed genes and differentially abundant serum proteins. The prioritized candidate molecule was further validated using serum ELISA, quantitative real-time PCR, Western blotting, hematoxylin and eosin staining, immunohistochemistry, and immunofluorescence co-staining in human serum and aortic tissue samples. Results: Transcriptomic analysis identified 1534 differentially expressed genes in aortic dissection tissues, while serum proteomic profiling identified 82 differentially abundant proteins associated with postoperative remodeling status. Cross-omics integration revealed seven overlapping molecules, among which PCSK9 was the only candidate showing concordant upregulation in both aortic dissection tissues and serum samples from patients with negative remodeling after TEVAR. Serum PCSK9 levels were significantly higher in patients with aortic dissection than in normal controls. PCSK9 mRNA and protein expression were also increased in human aortic dissection tissues. Histological and immunostaining analyses showed enhanced PCSK9 accumulation in the dissected aortic wall, particularly in medial regions with partial overlap with α-SMA-positive areas. Conclusions: PCSK9 was identified as a cross-omics prioritized candidate molecule associated with aortic dissection and negative remodeling after TEVAR. Its elevation in serum and aortic tissues, together with its enrichment in α-SMA-positive medial regions, suggests a potential link between circulating proteomic alterations and local aortic wall pathology. These findings support further investigation of PCSK9 as a candidate biomarker for adverse remodeling in TBAD.