秋水仙碱通过靶向巨噬细胞介导的白介素-6抑制作用，减轻心脏肥厚。

Abstract

HCM hearts undergo pro-fibrotic and pro-inflammatory microenvironment remodeling. • HCM hearts exhibit pro-inflammatory macrophage enrichment and elevated IL-6 levels. • Colchicine reduces IL-6 production in pro-inflammatory macrophages, attenuating fibrosis and HCM progression. • Our study provides the first preclinical evidence that colchicine alleviates myocardial inflammation and fibrosis in HCM. Hypertrophic cardiomyopathy (HCM), the most prevalent inherited cardiovascular disease, is strongly linked to progressive heart failure and sudden cardiac death (SCD). However, its underlying pathogenic mechanisms remain incompletely understood, and effective therapeutic strategies are still lacking. Here, we established two murine HCM models harboring high SCD risk–associated mutations. Single-cell RNA sequencing revealed immune activation and enhanced fibrotic remodeling in the myocardium of these models. Therefore, we hypothesized that colchicine, a widely used anti-inflammatory drug known to reduce cardiovascular events in multiple cardiac disorders, may also represent a promising therapeutic candidate for HCM. As we expected, colchicine treatment attenuated pathological remodeling in our study, as evidenced by reduced cardiomyocyte hypertrophy, decreased fibrosis, and downregulation of cardiac stress markers ( Anp, Bnp ) and fibrotic mediators ( Ctgf, Col1a1, Col3a1) . In addition, colchicine attenuated pro-inflammatory macrophage populations and suppressed IL-6 expression, thereby contributing to the preservation of cardiac function. These findings provide the first preclinical evidence that colchicine alleviates myocardial inflammation and fibrosis in HCM, underscoring its potential as a novel therapeutic strategy to reduce fibrosis, lower SCD risk, and improve patient outcomes. Download: Download high-res image (139KB) Download: Download full-size image