Fenofibrate unexpectedly induces cardiac hypertrophy in mice lacking MuRF1

Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology
Traci L ParryMonte S Willis

Abstract

The muscle-specific ubiquitin ligase muscle ring finger-1 (MuRF1) is critical in regulating both pathological and physiological cardiac hypertrophy in vivo. Previous work from our group has identified MuRF1's ability to inhibit serum response factor and insulin-like growth factor-1 signaling pathways (via targeted inhibition of cJun as underlying mechanisms). More recently, we have identified that MuRF1 inhibits fatty acid metabolism by targeting peroxisome proliferator-activated receptor alpha (PPARα) for nuclear export via mono-ubiquitination. Since MuRF1-/- mice have an estimated fivefold increase in PPARα activity, we sought to determine how challenge with the PPARα agonist fenofibrate, a PPARα ligand, would affect the heart physiologically. In as little as 3 weeks, feeding with fenofibrate/chow (0.05% wt/wt) induced unexpected pathological cardiac hypertrophy not present in age-matched sibling wild-type (MuRF1+/+) mice, identified by echocardiography, cardiomyocyte cross-sectional area, and increased beta-myosin heavy chain, brain natriuretic peptide, and skeletal muscle α-actin mRNA. In addition to pathological hypertrophy, MuRF1-/- mice had an unexpected differential expression in genes associated with the pleiotropic ef...Continue Reading

Citations

Mar 27, 2018·Journal of Hypertension·Hendrik Gremmels, Jaap A Joles
Jul 18, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Alon SimchovitzHermona Soreq
Aug 17, 2018·Journal of Cardiovascular Development and Disease·Saranya RaviJonathan C Schisler
Aug 17, 2020·Journal of Cellular and Molecular Medicine·Rujia MiaoJiangang Wang

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