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Published on: June 15, 2018
Analysis of mtDNA, miR-155 and BACH1 expression in hearts from donors with and without Down syndrome
Erik Hefti1, Adolfo Quiñones-Lombraña1, Almedina Redzematovic1
1a Department of Pharmaceutical Sciences, University at Buffalo , The State University of New York , Buffalo , NY , USA.
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 mtDNA(4977) 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 mtDNA(4977) deletion (DS(% frequency mtDNA(4977)) deletion: 0.0086 ± 0.0166 versus non-DS(% frequency mtDNA(4977)) 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.
Insights
Cancer patients with Down syndrome (DS) face higher risks of heart damage from chemotherapy. This study found altered mitochondrial DNA (mtDNA) in DS hearts, potentially explaining this increased cardiotoxicity risk.
Area of Science:
- Cardiology
- Genetics
- Oncology
Background:
- Patients with Down syndrome (DS) exhibit increased susceptibility to anthracycline-induced cardiotoxicity.
- Mitochondrial DNA (mtDNA) alterations are implicated in the pathogenesis of heart conditions.
Purpose of the Study:
- To investigate whether cardiac mtDNA alterations contribute to anthracycline-related cardiotoxicity in Down syndrome (DS) patients.
- To examine the expression of BACH1 and microRNA-155 (miR-155) in DS hearts.
Main Methods:
- Quantification of cardiac mtDNA and the common mtDNA(4977) deletion in heart samples from individuals with and without DS.
- Analysis of BACH1 and miR-155 gene expression in cardiac tissues.
Main Results:
- Heart samples from DS patients showed significantly lower levels of mtDNA and a higher frequency of the mtDNA(4977) deletion compared to non-DS controls.
- No significant differences in BACH1 and miR-155 expression were observed between DS and non-DS hearts.
- An association between BACH1 and miR-155 expression was found in non-DS hearts, suggesting potential alterations in DS.
Conclusions:
- Mitochondrial DNA (mtDNA) alterations, specifically reduced mtDNA quantity and increased mtDNA(4977) deletion, are present in the hearts of individuals with Down syndrome (DS).
- These mtDNA changes may underlie the heightened risk of anthracycline-related cardiotoxicity in DS cancer patients.
- While BACH1 and miR-155 expression levels were similar, their interaction patterns may differ in DS hearts, warranting further investigation.
