Potential Diagnostic and Therapeutic Uses of DPT in Acute Type A Aortic Dissection.

摘要

PURPOSE: Acute Type A aortic dissection (ATAAD) is a catastrophic cardiovascular emergency with high mortality and few treatment options. Diagnostic biomarkers or targeted treatments remain in the rudimentary stage, complicating early detection and intervention. The aim is to discover novel diagnostic and therapeutic biomarkers for ATAAD through integrated bioinformatics and experimental validation. METHODS: Differentially expressed genes (DEGs) were identified using the "limma" package in R, applying the combined, normalized, and batch-effect-corrected microarray datasets GSE52093 and GSE98770. Functional enrichment analyses (GO and KEGG), protein-protein interaction (PPI) network construction, and weighted gene coexpression network analysis (WGCNA) were performed to identify key genes. Key genes were validated by qPCR, immunofluorescence, and functional assays in human aortic smooth muscle cells (HASMCs) and an independent dataset (GSE153434). RESULTS: There were 441 DEGs with 164 upregulated and 277 downregulated genes. These hub genes also overlapped with four key genes (DPT, ITGA5, HGF, and PLAUR) in the key WGCNA module. Of these, DPT was downregulated compared with ATAAD tissues. DPT knockdown induced HASMC migration and inhibited HASMC proliferation, as assessed by functional assays. The diagnostic potential of these genes, especially of DPT, was confirmed using ROC analysis. CONCLUSION: DPT is a promising diagnostic and therapeutic biomarker for ATAAD. Downregulation may also disturb extracellular matrix homeostasis and smooth muscle cell function, leading to aortic wall instability. These findings provide a foundation for future research on DPT-targeted interventions for ATAAD.