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J Am Coll Cardiol, 2004; 43:68-76, doi:10.1016/j.jacc.2003.07.030
© 2004 by the American College of Cardiology Foundation
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The cardiac atria are chambers of active remodeling and dynamic collagen turnover during evolving heart failure

Anjum Khan, MSc*, Gordon W. Moe, MD, FACC*, Nafiseh Nili, PhD*, Effat Rezaei, PhD*, Muhammad Eskandarian, MD*, Jagdish Butany, MD{dagger} and Bradley H. Strauss, MD, PhD, FACC*,*

* Roy and Ann Foss Interventional Cardiology Research Program, Terrence Donnelly Heart Center, St. Michael's Hospital, Toronto, Ontario, Canada
{dagger} University Health Network, University of Toronto, Toronto, Ontario, Canada



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Figure 1 (Upper panel) Representative Western blot for degraded collagen in an right atrium with severe heart failure (HF). Lanes 1 to 4 are controls. Lanes 5 to 8 are severe HF. (Lower panel) Group data from densitometric analysis. *p < 0.01 versus control.

 


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Figure 2 Gelatin zymograms of gelatinase activity in the left atrium of control and heart failure (HF) animals. (Upper panels) Early HF. (Lower panels) Severe HF. On the left panels, lanes 1 to 4 represent controls, and lanes 5 to 8 are HF. In early HF, pro- and active matrix metalloproteinases (MMP)-9 are increased, while MMP-2 activity is not significantly changed. In severe HF, pro- and active MMP-2 are significantly increased, while MMP-9 activity is not significantly changed. The corresponding densitometry is shown in the right panels. *p < 0.05 versus respective controls.

 


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Figure 3 (A) Quantitative gelatinase assay. (Left panels) Comparison between early heart failure (HF) and respective controls. (Right panels) Comparison between severe HF and respective controls. (Upper panels) Left atrium (LA). (Lower panels) Right atrium (RA). *p < 0.01 versus respective controls; {dagger}p = 0.05 versus control. (B) Effect of protease inhibition on gelatinase activity. Data are means of triplicate assays. There is 100% inhibition of gelatinase activity with GM6001, an matrix metalloproteinases inhibitor.

 


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Figure 4 Representative photomicrographs of myocytes in left atrium and right atrium stained with H & E stain (x20). The nuclei stain blue and the cytoplasm red. HF = heart failure.

 


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Figure 5 Representative photomicrographs of left atrium and right atrium stained with picrosirius red (x20). Collagen fibers stain deep red. HF = heart failure.

 


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Figure 6 Representative photomicrographs of terminal deoxy nucleotidyl transferase (TdT)-mediated dUTP-biotin nick-end labeling assay. The green stain overlapping red nuclei (arrows) indicates apoptotic nuclei. HF = heart failure.

 


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Figure 7 Correlations in severe heart failure. (A) Mean pulmonary artery pressure (mPAP) and gelatinase activity. (B) The left atrium (LA) wall tension index and collagen synthesis. (C) The LA wall tension index and gelatinase activity.

 




 
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