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- W2246112897 abstract "The goal of this study was to determine if proteasome inhibition (PI) could regress pre-existing hypertrophy and collagen accumulation. Mice were submitted to transverse aortic banding (B) for 3 weeks and compared to shams (S). Two weeks after B, mice were treated daily with the proteasome inhibitor epoxomicin (E, 0.5 mg/kg) or with the vehicle (V). After 3 weeks B, B-V showed an increase in proteasome activity (PA: 347±19in B-V vs.114±7 in S, P<0.05), and left ventricle/tibial length (LV/TL: 10.2±0.56 in B-V vs.6.2±0.3 in S, P<0.05). B-V mice developed signs of heart failure shown by a decreased ejection fraction (EF: 50±4 in B-V vs. 75±2 in S P<0.05). Compared to the B-V, B-E mice showed significantly lower PA (85±5, p<0.05 vs. B-V) and LV/TL (8.4±0.3, P<0.05 vs. B-V), and a better EF (62±4, P<0.05 vs. B-V). Because pressure overload activates the expression of collagen and matrix metalloproteases (MMP), we tested whether E would prevent this activation. Transcripts of collagen type 1 and MMP2 increased 4-fold in B-V versus sham (P<0.05), which was abolished in B-E. As a result, accumulation of interstitial collagen after B was lower in B-E versus B-V (1.6±0.8 in B-E vs. 9.0±0.5 in B-V, P<0.05). Therefore, PI started after B rescues ventricular function and decreases myocyte hypertrophy and collagen accumulation." @default.
- W2246112897 created "2016-06-24" @default.
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- W2246112897 date "2008-03-01" @default.
- W2246112897 modified "2023-09-25" @default.
- W2246112897 title "Improvement of cardiac contractile function by proteasome inhibition after pressure overload" @default.
- W2246112897 doi "https://doi.org/10.1096/fasebj.22.1_supplement.970.9" @default.
- W2246112897 hasPublicationYear "2008" @default.
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