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2009 Southern Regional Meeting Abstracts
Session: Cardiovascular Club
OVEREXPRESSION OF DOMINANT NEGATIVE TRANSFORMING GROWTH FACTOR (TGF)-β TYPE II RECEPTOR (DnTGFβRII) ATTENUATES PRESSURE OVERLOAD-INDUCED CARDIAC REMODELING AND DYSFUNCTION
Lucas JA, Miller AP, Zhang Y, Li P, Oparil S, Chen Y. University of Alabama at Birmingham, Birmingham, AL.
Purpose of Study: We have previously used a transgenic mouse model that expresses an inducible DnTGFβRII to demonstrate that blocking TGF-β signaling reduces pressure overload-induced interstitial collagen deposition in the heart. The current study utilized DnTGFβRII mice to test the hypothesis that collagen deposition in the pressure overloaded heart is required to maintain structure and prevent left ventricular (LV) dilation and dysfunction.
Methods Used: 8-10 wk old DnTGFβRII and nontransgenic control (NTG) mice were given 25 mM ZnSO4 in drinking water to induce the expression of DnTGFβRII gene 1 wk prior to transverse aortic constriction (TAC). 120 days after TAC or sham operation, LV mass, dimension and function were assessed by echocardiography. LV interstitial collagen content was assessed in picrosirius red stained sections by light microscopy.
Summary of Results: LV end diastolic and systolic diameters (LVEDD and LVESD) were significantly increased in Zinc treated DnTGFβRII mice after TAC, while ejection fraction (EF) and fractional shortening (FS) were significantly decreased in this group compared to the other five treatment groups (Table). The DnTGFβRII group receiving H2O only did not differ from NTG mice in any parameter. TAC induced collagen deposition was significantly attenuated in the TAC-DnTGFβRII+Zinc mice only.
Conclusions: These data support the hypothesis that intact endogenous TGF-β signaling is required to protect against LV dilation and dysfunction in the presence of pressure overload stress.
| NTG Mice | DnTGFβRII Mice | | Treatment | H2O + Sham (6) | H2O + TAC (6) | ZnSO4 + TAC (7) | H2O + Sham (6) | H2O + TAC (12) | ZnSO4 + TAC (9) | | BW | 30.6±0.5 | 36.1±1.9 | 33.1±2.2 | 30.3±0.8 | 32.8±2.0 | 31.2±1.4 | | LVEDD | 3.7±0.10 | 3.9±0.1 | 3.8±0.1 | 3.5±0.0 | 3.9±0.1* | 4.6±0.2*#Δ | | LVESD | 1.8±0.1 | 2.4±0.2* | 2.5±0.1* | 1.6±0.1 | 2.3±0.1* | 3.3±0.1*#Δ | | EF | 80.2±1.4 | 64.8±.6.6* | 65.9±3.9* | 81.8±.2.3 | 71.3±.3.0* | 50.8±.3.3*# | | FS | 48.0±1.4 | 36.4±5.5 | 36.2±2.9*# | 49.4±2.5 | 40.9±2.6* | 26.1±2.0*#Δ | | Collagen % total area | - | 5.8±0.8 | 7.9±0.8 | - | 5.6±0.6 | 0.8±0.1#Δ |
Results are means±SEM. The normalized chamber sizes were determined by ANCOVA with BW as a covariate. * p<0.05 vs. respective sham mice; # p<0.05 vs. respective NTG mice; Δ p<0.05 vs. respective H2O mice.
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