Mitochondrial Aging: Focus on Mitochondrial DNA Damage in Atherosclerosis - A Mini-Review

Sobenin, Igor A.; Zhelankin, Andrey V.; Sinyov, Vasily V.; Bobryshev, Yuri V.; Orekhov, Alexander N.

doi:10.1159/000368923

Cited by 32 publications

(21 citation statements)

References 54 publications

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“…30 Aging may lead to atherosclerosis via increased levels of oxidative stress, DNA damage, mitochondrial dysfunction, and altered balance of cell proliferation and apoptosis. 31 …”

Section: Discussionmentioning

confidence: 99%

Optimal Prediction of Carotid Intraplaque Hemorrhage Using Clinical and Lumen Imaging Markers

McLaughlin

Hinckley

Treiman

et al. 2015

AJNR Am J Neuroradiol

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Purpose MRI detects intraplaque hemorrhage (IPH) with high accuracy using the magnetization-prepared rapid acquisition gradient echo (MPRAGE) sequence. Still, MRI is not readily available for all patients, and many receive CTA instead. Our goal was to determine essential clinical and lumen imaging predictors of IPH as indicators of its presence and clues to its pathogenesis. Methods In this retrospective cross sectional study, patients undergoing stroke workup with MRI/MRA underwent carotid IPH imaging. A total of 726 carotid plaques were analyzed, excluding vessels with non-carotid stroke sources (420), occlusions (7), or near-occlusions (3). Potential carotid imaging predictors of IPH included percent diameter and mm stenosis, plaque thickness, ulceration, and intraluminal thrombus. Clinical predictors were recorded and a multivariable logistic regression model was fitted. Backward-elimination was used to determine essential IPH predictors with a threshold two-sided p<.10. Receiver operating characteristic (ROC) analysis was also performed. Results Predictors of carotid IPH included plaque thickness (odds ratio, OR=2.20, p<.001), mm stenosis (OR=0.46, p<.001), ulceration (OR=4.25, p=.020), age (OR=1.11, p=.001) and male sex (OR=3.23, p=.077). The final model discriminatory value was excellent (area under the curve, AUC=0.932). This was significantly higher than models using only plaque thickness (AUC=0.881), mm stenosis (AUC=0.830) or ulceration (AUC=0.715) p<.001. Conclusions Optimal discrimination of carotid IPH requires information on plaque thickness, mm stenosis, ulceration, age and male sex. These factors predict IPH with high discriminatory power, and may provide clues to the pathogenesis of IPH. This model could be used to predict the presence of IPH when MRI is contraindicated.

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“…30 Aging may lead to atherosclerosis via increased levels of oxidative stress, DNA damage, mitochondrial dysfunction, and altered balance of cell proliferation and apoptosis. 31 …”

Section: Discussionmentioning

confidence: 99%

Optimal Prediction of Carotid Intraplaque Hemorrhage Using Clinical and Lumen Imaging Markers

McLaughlin

Hinckley

Treiman

et al. 2015

AJNR Am J Neuroradiol

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“…This process has been implicated in several human diseases including atherosclerosis and aging 1–3 . Studies from humans and animal models have confirmed that atherosclerosis and mtDNA damage increase exponentially with aging 4–6 , and mitoOS level correlates with atherosclerotic lesion progression during aging 5, 7 . We previously showed that excessive mitoOS in atherosclerotic lesional myeloid cells (macrophages) accelerated lesion development via enhanced inflammation and increased recruitment of monocytes in young Ldlr −/− mice 8 .…”

Section: Introductionmentioning

confidence: 94%

Mitochondrial Oxidative Stress Promotes Atherosclerosis and Neutrophil Extracellular Traps in Aged Mice

Wang

et al. 2017

ATVB

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Rationale Mitochondrial oxidative stress (mitoOS) has been shown to be increased in various cell types in human atherosclerosis and with aging. However, the role of cell type-specific mitoOS in atherosclerosis in the setting of advanced age and the molecular mechanisms remain to be determined in vivo. Objective The aim of this study was to examine the role of myeloid-cell mitoOS in atherosclerosis in aged mice. Approach and Results Lethally irradiated Ldl receptor-deficient mice (Ldlr−/−) were reconstituted with bone marrow from either wild type or mitochondrial catalase (mCAT) mice. mCAT transgenic mice contain ectopically expressed human catalase gene in mitochondria, which reduces mitoOS. Starting at the age of 36 weeks, mice were fed the Western-type diet (WD) for 16 weeks. We found that mitoOS in lesional myeloid cells was suppressed in aged mCAT→Ldlr−/− chimeric mice compared to aged controls, and this led to a significant reduction in aortic root atherosclerotic lesion area despite higher plasma cholesterol levels. Neutrophil extracellular traps (NETs), a pro-inflammatory extracellular structure that contributes to atherosclerosis progression, were significantly increased in the lesions of aged mice compared with lesions of younger mice. Aged mCAT→Ldlr−/− mice had less lesional neutrophils and decreased NETs compared with age-matched WT→Ldlr−/− mice, while young mCAT→ and WT→ Ldlr−/− mice had comparable numbers of neutrophils and similar low levels of lesional NETs. Using cultured neutrophils, we showed that suppression of mitoOS reduced 7-ketocholesterol-induced NET release from neutrophils of aged but not younger mice. Conclusions MitoOS in lesional myeloid cells enhanced atherosclerosis development in aged mice, and this enhancement was associated with increased lesional NETs. Thus, mitoOS-induced NET formation is a potentially new therapeutic target to prevent atherosclerosis progression during aging.

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“…During atherosclerosis progression, blood vessels are bombarded by different types of stresses. For example, high blood tension, glucose, and oxidized LDL (oxLDL) cause human endothelial dysfunction via a variety of oxidative stresses . In addition, endothelial cells become more sensitive to oxidative stress induced endothelial dysfunction , indicating that aging represses the endogenous protective ability of endothelial cells under oxidative attack.…”

Section: Introductionmentioning

confidence: 99%

Quercetin is a potent anti‐atherosclerotic compound by activation of SIRT1 signaling under oxLDL stimulation

Hung

Chan

Chu

et al. 2015

Molecular Nutrition Food Res

132

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Mitochondrial Aging: Focus on Mitochondrial DNA Damage in Atherosclerosis - A Mini-Review

Cited by 32 publications

References 54 publications

Optimal Prediction of Carotid Intraplaque Hemorrhage Using Clinical and Lumen Imaging Markers

Optimal Prediction of Carotid Intraplaque Hemorrhage Using Clinical and Lumen Imaging Markers

Mitochondrial Oxidative Stress Promotes Atherosclerosis and Neutrophil Extracellular Traps in Aged Mice

Quercetin is a potent anti‐atherosclerotic compound by activation of SIRT1 signaling under oxLDL stimulation

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