July 31, 2026Journal of the American College of Cardiology109 citations
View Full PaperUpregulation of the Bcl-2 family of proteins in end stage heart failure
Key Result
End stage heart failure (DCM and IHD) was associated with significantly higher levels of proapoptotic and antiapoptotic Bcl-2 proteins and TUNEL-positive cells compared with normal donors.
Key Points
- This research investigates the expression of Bcl-2 family proteins and their correlation with markers of apoptosis in heart failure.
- Analyzed expression of Bcl-2 family proteins in patients with dilated cardiomyopathy and ischemic heart disease.
- Used TUNEL assay to assess DNA fragmentation and differentiate between apoptosis and necrosis.
- Performed Western blot analysis and immunocytochemistry to measure protein levels.
- Significantly higher levels of proapoptotic and antiapoptotic proteins were found in diseased groups compared to normal donors.
- Bax levels were significantly elevated in the ischemic heart disease group compared to dilated cardiomyopathy.
- Higher percentage of TUNEL-positive cells in diseased groups indicated ongoing apoptosis.
Study Design
Type
Observational
PICO
P
Population
End stage heart failure (dilated cardiomyopathy and ischemic heart disease)
E
Exposure / Comparator
End stage heart failure (DCM and IHD) vs Normal donors
O
Primary Outcome
Expression of proapoptotic and antiapoptotic Bcl-2 proteins and percentage of TUNEL-positive cells
Abstract
OBJECTIVES: To elucidate the pattern of expression of four members of the Bcl-2 family of proteins and to correlate this with terminal deoxynucleotidyl transferase TdT-mediated dUTP nick end labelling (TUNEL) and DNA fragmentation. BACKGROUND: Apoptosis has been implicated as a possible mechanism in the development of heart failure. However, the mechanisms involved remain unclear. METHODS: We have studied the expression of four members of the Bcl-2 family that are involved in the regulation of apoptosis and analyzed DNA fragmentation as a marker of apoptosis and as a biochemical criterion to distinguish between apoptosis and necrosis in dilated cardiomyopathy (DCM), ischemic heart disease (IHD) and normal donors. RESULTS: Western blot analysis and immunocytochemistry of the proapoptotic and antiapoptotic Bcl-2 proteins demonstrated significantly higher levels of all these proteins in the diseased groups compared with normal donors. Additionally, Bax was significantly higher in the IHD group compared with DCM. Terminal deoxynucleotidyl transferase TdT-mediated dUTP nick end labelling analysis demonstrated a significantly higher percentage of TUNEL-positive cells in the diseased groups compared with the control. Genomic DNA extraction of ventricular myocardial tissue showed no demonstrable DNA laddering for any of the groups. CONCLUSIONS: The significant increases in the levels of the proapoptotic proteins Bak and Bax and the higher percentage of TUNEL-positive cells in both diseased groups suggests the presence of ongoing apoptosis. However, increases in the antiapoptotic proteins, Bcl-2 and Bcl-xL, suggest a possible concomitant, compensatory antiapoptotic mechanism in patients with heart failure.