Analysis of mtDNA, miR-155 and BACH1 expression in hearts from donors with and without Down syndrome

Abstract

Cancer patients with Down syndrome (DS) are at increased risk for anthracycline-related cardiotoxicity. Mitochondrial DNA (mtDNA) alterations in hearts with-DS may contribute to anthracycline-related cardiotoxicity. Cardiac mtDNA and the mtDNA⁴⁹⁷⁷ deletion were quantitated in samples with- (n = 11) and without-DS (n = 31). Samples with-DS showed 30% lower mtDNA (DS_{MT-ND1/18Sratio}: 1.48 ± 0.72 versus non-DS_{MT-ND1/18Sratio}: 2.10 ± 1.59; p = 0.647) and 30% higher frequency of the mtDNA⁴⁹⁷⁷ deletion (DS_{% frequency mtDNA⁴⁹⁷⁷ deletion}: 0.0086 ± 0.0166 versus non-DS_{% frequency mtDNA⁴⁹⁷⁷ deletion}: 0.0066 ± 0.0124, p = 0.514) than samples without-DS. The BACH1 and microRNA-155 (miR-155) genes are located in chromosome 21, and their products have demonstrated roles during oxidative stress. BACH1 and miR-155 expression did not differ in hearts with- and without-DS. An association between BACH1 and miR-155 expression was detected in hearts without-DS, suggesting alterations between BACH1-miR-155 interactions in the DS settings.

• Anthracycline-related cardiotoxicity
• Down syndrome
• mitochondrial DNA
• oxidative stress

Declaration of interest

The authors declare that there are no conflicts of interest. This work was supported by the National Institute of General Medical Sciences [GM073646].