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- W884424881 abstract "The ubiquitin proteasome system is a protein degradation system mediated in part by the muscle ring finger-1 (MuRF1) ubiquitin ligase. MuRF1 has been shown to play an important role in cardiac hypertrophy. MuRF1 also targets and inhibits PPAR-α activity, with MuRF1-/- hearts showing increased PPAR-α activity in vivo. The unique duality of MuRF1′s regulation of cardiac hypertrophy and PPAR-α's activity led us to determine the in vivo effect of MuRF1 on PPAR-α signaling. This was done by challenging them with fenofibrate, a PPAR-α agonist. MuRF1-/- and age matched sibling MuRF1+/+ controls received standard chow or fenofibrate chow (0.5% w/w). Echocardiography determined cardiac function at 3 and 8 weeks, followed by cardiac tissue analysis by RT-PCR, histology, and electron microscopy. Fenofibrate induced a time dependent increase in cardiac hypertrophy, evidenced by significant (P<0.05) increases in cardiac wall thickness and cardiomyocyte cross sectional area in MuRF1-/- mice (25% increase vs MuRF1+/+). Pathological hypertrophy genes beta-myosin heavy chain, smooth muscle alpha-actin, and brain natriuretic peptide were also increased in fenofibrate fed MuRF1-/- mice. Additionally, fenofibrate fed MuRF1-/- mice exhibited increased lipid filled vesicles in and around mitochondria as well as increased mitochondrial fallout compared to fenofibrate fed MuRF+/+ mice. These findings suggest that cardiac hypertrophy associated with PPAR-α agonist fed MuRF1-/- mice appear to be pathological in nature. These data also show, for the first time, the interplay between MuRF1, PPAR-α, and hypertrophic cardiomyopathy pathways, indicating a unique role for PPAR-α in cardiac hypertrophy." @default.
- W884424881 created "2016-06-24" @default.
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- W884424881 date "2015-04-01" @default.
- W884424881 modified "2023-10-16" @default.
- W884424881 title "Cardiac MuRF1 regulates PPAR‐α agonist‐induced spontaneous cardiac hypertrophy in vivo" @default.
- W884424881 doi "https://doi.org/10.1096/fasebj.29.1_supplement.1043.12" @default.
- W884424881 hasPublicationYear "2015" @default.
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