C-C motif receptor 2 is a core profibrotic factor in uremic cardiomyopathy

作者：Bao JF, Guo BC, Mo JJ, Zhu H, Jia N, Hou F, Liu Y, Li A · 发表于：Disease models & mechanisms · 年份：2026 · DOI：10.1242/dmm.052395 · 被引用次数：72 · 研究领域：Cardiomyopathies、Uremia、Receptors, CCR2、Animals、Fibrosis、Humans、Myocardium、Male、Macrophages、Disease Models, Animal、Mice, Inbred C57BL、Extracellular Matrix

Uremic cardiomyopathy (UC) represents a leading cause of mortality in patients with chronic kidney disease (CKD), characterized by left ventricular hypertrophy (LVH) and fibrosis. The underlying mechanisms of UC pathogenesis remain incompletely understood. This study developed two methods to simulate human UC - modified nephrectomy (MNx) and adenine-normal combinational diet - and compared these approaches across several rodent strains. Transcriptomic analysis was performed on left ventricular tissues from these models. The analysis revealed global changes in UC, including dysregulated cell cycle processes, enhanced extracellular matrix remodeling and metabolic abnormalities, while also highlighting molecular distinctions between MNx- and adenine-induced UC. Notably, this study identified C-C-motif receptor 2 (CCR-2) as a novel potential antifibrotic target in UC. CCR-2 blockade substantially reversed fibrosis without affecting LVH. The mechanism through which CCR-2 inhibition suppresses cardiac fibrosis development in UC appears to involve the promotion of cardiac residual macrophage expansion. These findings establish a central role for CCR-2 in cardiac fibrosis and suggest CCR-2 inhibition as a promising therapeutic target for UC.