2013
DOI: 10.1161/circulationaha.113.002271
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Mitochondrial DNA Damage Can Promote Atherosclerosis Independently of Reactive Oxygen Species Through Effects on Smooth Muscle Cells and Monocytes and Correlates With Higher-Risk Plaques in Humans

Abstract: Background— Mitochondrial DNA (mtDNA) damage occurs in both circulating cells and the vessel wall in human atherosclerosis. However, it is unclear whether mtDNA damage directly promotes atherogenesis or is a consequence of tissue damage, which cell types are involved, and whether its effects are mediated only through reactive oxygen species. Methods and Results— mtDNA damage occurred early in the vessel wall in apolipoprotein E–null (ApoE… Show more

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Cited by 237 publications
(196 citation statements)
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“…The resulting defect in proofreading function results in widespread mtDNA point mutations and deletions (Trifunovic et al., 2004). Indeed, PolG mice show extensive mtDNA damage and reduced mitochondrial respiration in their aortas and cultured VSMCs, with no change in ROS early in life (Yu et al., 2013). PolG mice showed multiple features of progeria, including kyphosis and greying of fur, and became too frail to survive instrumentation beyond 32 wk; we therefore examined vascular aging markers between 8 and 32 wk of age in both WT and PolG mice.…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…The resulting defect in proofreading function results in widespread mtDNA point mutations and deletions (Trifunovic et al., 2004). Indeed, PolG mice show extensive mtDNA damage and reduced mitochondrial respiration in their aortas and cultured VSMCs, with no change in ROS early in life (Yu et al., 2013). PolG mice showed multiple features of progeria, including kyphosis and greying of fur, and became too frail to survive instrumentation beyond 32 wk; we therefore examined vascular aging markers between 8 and 32 wk of age in both WT and PolG mice.…”
Section: Resultsmentioning
confidence: 99%
“…To dissect the role of mtDNA‐mediated mitochondrial dysfunction in vascular aging, we examined mice with specific mtDNA manipulations that do not change vascular ROS at the time points studied (Yu et al., 2013, 2017). Both mtCN and mitochondrial respiration were reduced markedly by 44 wk in WT mice, concurrent with physiological and structural markers of vascular aging.…”
Section: Discussionmentioning
confidence: 99%
“…TRF2 protein is regulated by ubiquitin-mediated degradation, in part by the p53-induced E3 ubiquitin ligase Siah-1. 25 VSMCs in plaques are characterized by multiple forms of DNA damage, including double-and single-strand breaks, oxidative lesions, and mtDNA damage 37,38 ; DNA damage markers and activation of multiple DNA repair pathways are maintained in cultured plaque VSMCs. 7,20,38 Plaque VSMCs in culture and cells expressing α-SMA in human plaques showed downregulated TRF2 associated with markers of both DNA damage (γ-H2AX) and DNA repair (p-ATM).…”
Section: Discussionmentioning
confidence: 99%
“…However, such controls do not appear to have been carried out. 1 In addition, MitoB is not suitable for the assessment of superoxide anion, the primary ROS produced by mitochondria.…”
Section: To the Editormentioning
confidence: 99%
“…4 However, none of these recommendations have been experimentally validated in mice. 1,4,5 Therefore, even when assuming that the recommended procedure was followed by Yu et al, 1 the possibility that MitoB becomes oxidized to MitoP in the circulation, that is, before it enters cells within the aortic wall, has not been excluded, just as it is unclear whether reliable and pathologically meaningful information can be obtained from a single time point measurement.…”
Section: To the Editormentioning
confidence: 99%