Figure 6. Similar levels of DNA damage but mtDNA copy number analysis and RNA sequencing suggest a reduction in lesional mitochondrial activity in Apoe^−/−Neil3^−/− mice.

(A) Relative nuclear DNA damage and (B) relative mitochondrial DNA damage as evaluated by a qPCR-based method in liver (n = 7–9), aorta (n = 5–7) and plaques (n = 6–7). Values are normalized to nuclear and mitochondrial DNA damage in Apoe^−/− mice, respectively. (C,D) Accumulation of 8-oxodG and 5-OHdC in liver (n = 6–9) and aortas (n = 3–4), as evaluated by mass spectrometry. (E) Relative DNA damage level of promoter regions from Lcn2, Ucp1 and Lpl as evaluated by a qPCR-based method in liver (n = 8–9). Values are normalized to promoter DNA damage level in Apoe^−/− mice. (F) MtDNA copy number in liver (n = 7–9), aorta (n = 5–7) and plaques (n = 6–7) relative to the mtDNA levels in respective tissues of Apoe^−/− mice. In (C,D), aortic data are presented as mean ± SEM and were analyzed using Students’s t test. All other data in (A–F) are presented as median and interquartile range and were analyzed using Mann-Whitney U test; **p < 0.01. (G) Mitochondrial pathways significantly enriched in differentially expressed genes (DEGs) in aorta of Apoe^−/− and Apoe^−/−Neil3^−/− mice, as evaluated by RNA sequencing. (H) Gene ontology (GO) enrichment analyses of DEGs showing an overrepresentation of genes associated with mitochondrial compartments in Apoe^−/−Neil3^−/− as compared to Apoe^−/− mice.