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Physiological/hypertensive cardiac extracellular vesicles regulate fibroblast proteome in a sex dependent manner

ABSTRACT: The composition of cardiac EVs (cEVs) isolated from hypertensive mice and their capacity to reprogram cardiac fibroblasts was investigated using mass spectrometry-based proteomic profiling. Hypertensive and recovering cEVs displayed altered presence of proteins involved in peptidase activity, response to oxygen radical, and glycerolipid metabolism. Following their uptake to cardiac fibroblasts, cEV treatment from normotensive animals resulted in potent antifibrotic and prohomeostatic functions, with sex dependent differences in RNA splicing and energy metabolism proteins.Bioinformatic analysis of hypertensive-cEV remodelled fibroblasts revealed disease associated profibrotic signalling, and sex specific influences on components involved in antioxidant activity, RNA metabolism, fatty acid metabolism, and glycosylation processing. Moreover, investigation of temporal cEV signalling across hypertension and recovery revealed dynamic sex and disease dependent reprogramming of proteins related to RNA binding, interferon signalling, protein glycosylation, ECM regulation, signal transduction, and protein and energy metabolisms. We highlight the dynamic composition and signalling of cEVs in regulating fibroblast biology, reporting sex-dependent differences in cardiac physiology and hypertension.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Mus Musculus

SUBMITTER: David Greening

PROVIDER: MSV000092292 | MassIVE | Tue Jun 27 21:49:00 BST 2023

REPOSITORIES: MassIVE

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