Abstract

In the myocardium of control subjects and patients undergoing heart transplantation or left ventricular assist device implantation (LVAD), we analyzed concentrations of Al, As, Cd, Pb and Ni using inductively coupled plasma mass spectrometry. Myocardial generation of oxidative-stress-induced lipid peroxidation was analyzed by quantifying concentration of 4-Hydroxynonenal (4-HNE) with ELISA and pro-apoptotic DAPK2 gene expression was determined with quantitative RT-PCR. Compared to six control hearts, myocardial samples of 128 individuals undergoing heart transplantation or LVAD implantation exhibited a moderate increase in deposition of five tested non-essential elements, which was significantly increased only for Cd and cumulative deposition of Al, As, Cd, and Pb. Patients with higher cumulative deposition of Al, As, Cd, and Pb, underwent heart transplantation or LVAD implantation at a younger age than those with lower cumulative deposition, which was not observed in individual elements. Also, Al, As, and Ni exhibited a positive correlation with DAPK2 expression. Moreover, Al, As, Cd, and Ni showed positive correlations and Pb negative correlations with several mitochondrial quality control (MQC) genes. None of the elements showed correlation with 4-HNE generation in the myocardium. There was no difference in tested non-essential element deposition in dilated or ischemic cardiomyopathy. Patients with higher cumulative deposition of Al, As, Cd, and Pb in the myocardium underwent heart transplantation or LVAD implantation at a younger age, indicating that they may accelerate heart failure, which is associated with induction of DAPK2 expression. Deposition of Al, As, Cd, Ni, and Pb also altered the expression of several MQC genes.

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