Preventing hypocontractility-induced fibroblast expansion alleviates dilated cardiomyopathy.

ABSTRACT: Cardiomyocyte hypocontractility underlies inherited dilated cardiomyopathy (DCM). Yet, whether fibroblasts modify DCM phenotypes remains unclear despite their regulation of fibrosis, which strongly predicts disease severity. Expression of a hypocontractility-linked sarcomeric variant in mice triggered cardiac fibroblast expansion from the de novo formation of hyperproliferative mechanosensitized fibroblast states, which occurred prior to eccentric myocyte remodeling. Initially, this fibroblast response reorganized fibrillar collagen and stiffened the myocardium, albeit without depositing fibrotic tissue. These adaptations coincided with heightened matrix-integrin receptor interactions and diastolic tension sensation at focal adhesions within fibroblasts. Targeted p38 deletion arrested thes

SUBMITTER: Bretherton RC 

PROVIDER: S-EPMC12863455 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature