Dual itaconate delivery systems modulate macrophage Acod1-Hif-1α-glycolysis axis for immunotherapy of bioprosthetic heart valve calcification.

ABSTRACT: Calcification remains a major barrier to the long-term durability of bioprosthetic heart valves (BHVs), yet effective therapeutic strategies are still lacking. Emerging evidence suggests that targeting the immune response holds strong promise for mitigating BHV calcification, although the precise mechanisms remain elusive. Here, we integrated single-cell RNA sequencing, spatial transcriptomics, and multiple experimental models to elucidate the immunological mechanisms of BHV calcification and to develop targeted immunomodulatory strategies for anti-calcification therapy. The first spatiotemporal cell atlas of BHV calcification highlights macrophages as key immune drivers, confirmed by various immunodeficient mouse models. Notably, we identified a novel pro-calcification macrophage subset c

SUBMITTER: Wen S 

PROVIDER: S-EPMC12765066 | biostudies-literature | 2026 Apr

REPOSITORIES: biostudies-literature