CTHRC1 is a new therapeutic target and serum diagnostic biomarker for aortic dissection [Cthrc1_wt_ko_RNAseq]

Aortic dissection (AD) is a cardiovascular disease with rapid onset and extremely high short-term mortality, currently lacking specific peripheral blood-based biomarkers and effective treatments. Here, our analyses of AD samples from animal models and human patients revealed elevated blood levels of CTHRC1, a protein secreted by vascular fibroblasts. Furthermore, CTHRC1 regulates the phenotypic switch of vascular smooth muscle cells (VSMCs) during arterial remodeling by binding to ADAM9 on the VSMC membrane, activating the ERK1/2 signaling pathway, and promoting a contractile-to-synthetic transition. In Ang-II/BAPN induced AD mouse models, genetic ablation or antibody-mediated blockade of CTHRC1 effectively prevented AD formation and development. These findings unveil activated vascular fibroblast derived CTHRC1 as a critical regulator of VSMC phenotype and aortic structural integrity via the ERK1/2 signaling pathway, suggesting its potential as a novel serum diagnostic biomarker for AD diagnostic and a promising therapeutic target. Collectively, our data propose a new and effective strategy for diagnosis and clinical management of patients with AD.