Mural cell dysfunction contributes to diastolic heart failure by promoting endothelial dysfunction and vessel remodelling.

ABSTRACT:

Background

Heart failure with preserved ejection fraction (HFpEF) is a complex cardiovascular disease associated with metabolic comorbidities. Microvascular dysfunction has been proposed to drive HFpEF, likely via endothelial cell (EC) dysfunction, yet the role of the mural cells herein has never been explored.

Methods

We used the diabetic db/db mouse given 1% salt as a new model of HFpEF and crossed then with PDGFRβ^tg/tg-CreERT2-EYFP^tg/tg mice to label the mural cells. We combined single-cell RNA sequencing, NichetNet analysis and histology to determine the role of mural cell dysfunction in HFpEF.

Results

Db/db mice given 1% salt for 8 weeks developed diastolic dysfunction preceded by capillary density loss, pericyte loss and vessel regression.

SUBMITTER: Grootaert MOJ 

PROVIDER: S-EPMC11806843 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature