CTHRC1 is a new therapeutic target and serum diagnostic biomarker for aortic dissection
Description
Aortic dissection (AD) is a cardiovascular disease with rapid onset and an alarmingly high short-term mortality. Currently, there are no specific and rapid detection biomarkers based on peripheral blood or effective medications. In this study, we analyzed AD samples from mouse models and human patients, revealing a significant elevation of vascular fibroblast-derived exocrine protein CTHRC1 in the blood. Furthermore, single-cell analysis indicated that CTHRC1 regulates the phenotypic transformation of vascular smooth muscle cells (VSMCs) during arterial remodeling. By binding to ADAM9 receptor on the VSMC membrane, CTHRC1 activates the ERK1/2 signaling pathway, promoting the transformation of VSMCs from a contractile phenotype to a synthetic phenotype. Genetic ablation of CTHRC1 or blockade using anti-CTHRC1 monoclonal antibodies effectively prevented AD development in Ang-II/BAPN-induced mouse models. These findings unveil the critical role of CTHRC1 in regulating VSMC phenotypic switch and maintaining aortic structural integrity through the ERK1/2 pathway. Thus, CTHRC1 represents a novel serum diagnostic biomarker and a promising therapeutic target for AD.