Chronic therapy with metoprolol attenuates cardiomyocyte apoptosis in dogs with heart failure
Hani N. Sabbah, PhD, FACCa,
Victor G. Sharov, MD, PhDa,
Ramesh C. Gupta, PhDa,
Anastassia Todor, MDa,
Vinita Singh, PhDa and
Sidney Goldstein, MD, FACCa
a Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Heart and Vascular Institute, Detroit, Michigan, USA
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Figure 1 Panels A, B and C: Section of left ventricular myocardium showing cardiomyocytes bordering scar tissue from an untreated dog with heart failure (magnification x 750). (A) Shows a cardiomyocyte positively stained (red) with antimyosin antibody, identifying the cell as a cardiomyocyte. The unstained center region is the nucleus. (B) Shows the same cardiomyocyte nucleus stained positively (blue) with the specific nuclear stain Hoechst 33342. (C) Shows the same left ventricular section as in (A) and (B). The nucleus is positively stained (yellow-green) for nuclear DNA fragmentation.
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Figure 2 Bar graph (mean ± SEM) depicting endonuclease activity measured in left ventricular tissue homogenate prepared from six normal dogs (NL), six dogs with heart failure that were untreated (HF) and six dogs with HF treated with metoprolol (HF-MET).
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Figure 3 Western blot depicting the expression of calsequestrin (CSQ) in three normal (NL) dogs, three dogs with heart failure (HF) that were untreated and three dogs with HF treated with metoprolol (HF-MET).
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Figure 4 Top: Western blot depicting the expression of Bax in three normal (NL) dogs and three untreated dogs with heart failure (HF). Bottom: Western blot depicting the expression of Bax in three dogs with HF that were untreated and three dogs with HF treated with metoprolol (HF-MET). Western blots were performed at different times for MET-treated versus untreated dogs with HF and for untreated dogs with HF versus NL dogs and, therefore, while directionally consistent, the band density measurements are not directly comparable due to different exposure times.
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Figure 5 Top: Western blot depicting the expression of Bcl-2 in three normal (NL) dogs and three untreated dogs with heart failure (HF). Bottom: Western blot depicting the expression of Bcl-2 in five dogs with heart failure that were untreated (HF) and five dogs with HF that were treated with metoprolol (HF-MET). Western blots were performed at different times for MET-treated versus untreated dogs with HF and for untreated dogs with HF versus NL dogs and, therefore, while directionally consistent, the band density measurements are not directly comparable due to different exposure times.
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Figure 6 Top: Western blot depicting the expression of caspase-3 in three normal (NL) dogs and three untreated dogs with heart failure (HF). Bottom: Western blot depicting the expression of caspase-3 in three dogs with HF that were untreated (HF) and three dogs with HF that were treated with metoprolol (HF-MET). Western blots were performed at different times for MET-treated versus untreated dogs with HF and for untreated dogs with HF versus NL dogs and, therefore, while directionally consistent, the band density measurements are not directly comparable due to different exposure times.
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