Elevated DNase I Levels in Human Idiopathic Dilated Cardiomyopathy: an Indicator of Apoptosis?

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.