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Elevated DNase I levels in human idiopathic dilated cardiomyopathy: an indicator of apoptosis?
1Department of Anatomy and Histology, University of Sydney, New South Wales, Australia.
Insights
Deoxyribonuclease I (DNase I) levels are elevated in human heart failure patients with idiopathic dilated cardiomyopathy (IDCM). This finding suggests apoptosis may play a role in the pathophysiology of IDCM.
Area of Science:
- Biochemistry
- Cardiology
- Molecular Biology
Background:
- Deoxyribonuclease I (DNase I) is an enzyme involved in DNA degradation.
- The role of DNase I in cardiac tissue, particularly in heart failure, is not well understood.
Purpose of the Study:
- To determine DNase I levels in the human myocardium.
- To investigate the association between DNase I levels and end-stage heart failure due to idiopathic dilated cardiomyopathy (IDCM).
Main Methods:
- Analysis of left ventricular myocardial samples from 13 IDCM patients and 4 non-diseased donor hearts.
- Quantification of DNase I levels using a zymogram technique.
- Characterization of the enzyme's properties (e.g., pH dependence, cofactor requirements, inhibition by actin).
Main Results:
- Significantly elevated DNase I levels were observed in IDCM heart samples (1.69 +/- 0.22 pg/microgram protein) compared to non-diseased donor hearts (0.22 +/- 0.05 pg/microgram protein).
- The enzyme extracted from heart tissue exhibited characteristics consistent with DNase I, including dependence on Ca2+/Mg2+ and inhibition by Zn2+ and actin.
Conclusions:
- This is the first report demonstrating increased DNase I levels in the human myocardium of patients with IDCM.
- Elevated DNase I in IDCM suggests a potential role for apoptosis in the pathophysiology of this heart failure condition.
Abstract:
This is the first report to determine deoxyribonuclease I (DNase I) levels in the human myocardium and the first to demonstrate an increased DNase I level associated with end-stage heart failure due to idiopathic dilated cardiomyopathy (IDCM) compared to non-diseased heart samples. Left ventricular samples were obtained following transplantation from failing hearts of 13 patients diagnosed with IDCM and from four unused donor hearts. Using a zymogram technique, we show that the DNase I levels of the IDCM heart samples were significantly elevated (range 0.65-2.75 pg DNase I/microgram protein, mean +/- S.E. of 1.69 +/- 0.22 pg/micrograms) compared to four non-diseased, donor heart samples (range 0.12-0.35 pg/microgram protein, mean +/- S.E. of 0.22 +/- 0.05 pg/microgram). The DNase I extracted from heart tissue was characterized by: (1) a co-migration with bovine pancreatic DNase I; (2) a pH dependence consistent with DNase I; (3) a dependence of its activity on both Ca2+ and Mg2+ and an inhibition by Zn2+; and (4) an inhibition of its activity in the presence of monomeric rabbit skeletal muscle actin. The elevated DNase I levels associated with heart failure due to IDCM suggests that apoptosis may be implicated in pathophysiology of this disorder.