Heart failure-specific cardiac fibroblasts contribute to cardiac dysfunction via the MYC-CXCL1-CXCR2 axis.

ABSTRACT: Heart failure (HF) is a growing global health issue. While most studies focus on cardiomyocytes, here we highlight the role of cardiac fibroblasts (CFs) in HF. Single-cell RNA sequencing of mouse hearts under pressure overload identified six CF subclusters, with one specific to the HF stage. This HF-specific CF population highly expresses the transcription factor Myc. Deleting Myc in CFs improves cardiac function without reducing fibrosis. MYC directly regulates the expression of the chemokine CXCL1, which is elevated in HF-specific CFs and downregulated in Myc-deficient CFs. The CXCL1 receptor, CXCR2, is expressed in cardiomyocytes, and blocking the CXCL1-CXCR2 axis mitigates HF. CXCL1 impairs contractility in neonatal rat and human iPSC-derived cardiomyocytes. Human CFs from failing hear

SUBMITTER: Komuro J 

PROVIDER: S-EPMC12436193 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature