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

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.

搜集汇总

背景与挑战

背景概述

该数据集聚焦于主动脉夹层（AD）的研究，揭示了血管成纤维细胞来源的外分泌蛋白CTHRC1在血液中显著升高，可作为新的血清诊断生物标志物。研究发现CTHRC1通过激活ERK1/2信号通路调节血管平滑肌细胞表型转化，并证明其作为治疗靶点，通过遗传敲除或抗体阻断可有效预防AD发展。