Role of mitochondrial DNA variants and copy number in diabetic atherogenesis

Chien, M C; Huang, Wen-Te; Wang, P W; Liou, Chia‐Wei; Lin, Tsu-Kung; Hsieh, Ching‐Chuan; Weng, Shao‐Wen

doi:10.4238/2012.september.17.4

Cited by 20 publications

(17 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our previous study, we found that diabetic atherogenesis is associated with decreased levels of mtDNA (Chien et al, 2012). The results of the present study showed that although HMGB1 may act as an inflammatory mediator based on its positive correlation with the expression of oxidative stress markers (8-OHdG and MDA), a proinflammatory marker (VCAM-1), and inflammatory markers (CD3 and CD68) both in the intima and the media of vessels, an HMGB1-related compensation mechanism may also function in diabetic patients with PAOD.…”

Section: Discussionmentioning

confidence: 91%

Expression of high-mobility group box protein 1 in diabetic foot atherogenesis

et al. 2015

Self Cite

View full text Add to dashboard Cite

ABSTRACT. The role of high mobility group box 1 (HMGB1) has been demonstrated in stroke and coronary artery disease but not in peripheral arterial occlusive disease (PAOD). The pathogenesis of HMGB1 in acute and chronic vascular injury is also not well understood. We hypothesized that HMGB1 induces inflammatory markers in diabetic PAOD patients. We studied 36 diabetic patients, including 29 patients with PAOD, who had undergone amputation for diabetic foot and 7 nondiabetic patients who had undergone amputation after traumatic injury. Expression of HMGB1 and inflammatory markers were quantified using immunohistochemical staining. Mitochondrial DNA copy number was quantified using real-time polymerase chain reaction. Compared with that in the traumatic amputation group, HMGB1 expression in vessels was significantly higher in the diabetes and diabetic PAOD groups. In all subjects, arterial stenosis grade was positively correlated with the expression levels of HMGB1, 8-hydroxyguanosine, malondialdehyde, vascular cell adhesion molecule 1, and inflammatory markers CD3, and CD68 in both the intima and the media of vessels. Furthermore, HMGB1 expression level was positively correlated with 8-hydroxyguanosine, vascular cell adhesion molecule 1, nuclear factorkB, CD3, and CD68 expression. Within the PAOD subgroup, subjects with HMGB1 expression had higher expression of the autophagy marker LC3A/B and higher mitochondrial DNA copy number. HMGB1 may be an inflammatory mediator with roles in oxidative damage and proinflammatory and inflammatory processes in diabetic atherogenesis. Moreover, it may have dual effects by compensating for increased mitochondrial DNA copy number and increased autophagy marker expression.

show abstract

Section: Discussionmentioning

confidence: 91%

Expression of high-mobility group box protein 1 in diabetic foot atherogenesis

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…In particular, mtDNA copy number is a key functional parameter that varies greatly between different cell or tissues types, both in response to overall metabolic and bioenergetics demands and as a consequence or cause of specific physiological and pathological conditions. Alterations in mtDNA copy number have been related to aging (He et al, 2014), cancer , neurodegenerative diseases (Podlesniy et al, 2013), diabetes (Chien et al, 2012) and other mitochondrial-related diseases (Liu et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Tissue-specific mtDNA abundance from exome data and its correlation with mitochondrial transcription, mass and respiratory activity

et al. 2015

View full text Add to dashboard Cite

Eukaryotic cells contain a population of mitochondria, variable in number and shape, which in turn contain multiple copies of a tiny compact genome (mtDNA) whose expression and function is strictly coordinated with the nuclear one. mtDNA copy number varies between different cell or tissues types, both in response to overall metabolic and bioenergetics demands and as a consequence or cause of specific pathological conditions. Here we present a novel and reliable methodology to assess the effective mtDNA copy number per diploid genome by investigating off-target reads obtained by whole-exome sequencing (WES) experiments. We also investigate whether and how mtDNA copy number correlates with mitochondrial mass, respiratory activity and expression levels. Analyzing six different tissues from three age- and sex-matched human individuals, we found a highly significant linear correlation between mtDNA copy number estimated by qPCR and the frequency of mtDNA off target WES reads. Furthermore, mtDNA copy number showed highly significant correlation with mitochondrial gene expression levels as measured by RNA-Seq as well as with mitochondrial mass and respiratory activity. Our methodology makes thus feasible, at a large scale, the investigation of mtDNA copy number in diverse cell-types, tissues and pathological conditions or in response to specific treatments.

show abstract

“…72 Diabetes is one of the major risk factors for atherosclerosis, and there is a report that diabetic atherogenesis is associated with decreased mtDNA copy number. 73 …”

Section: Consequences Of Excessive Mtrosmentioning

confidence: 99%

Emerging Roles of Mitochondria ROS in Atherosclerotic Lesions: Causation or Association?

Wang

Tabas

2014

JAT

View full text Add to dashboard Cite

Mitochondrial-derived reactive oxygen species (mtROS) is one of the major sources of cellular ROS, and excessive mtROS is associated with atherosclerosis progression in both human and mouse models. This review aims to summarize the most recent studies showing the existence, the causes and pathological consequences of excessive mtROS in atherosclerosis. Despite numerous association and causation studies demonstrating the importance of mtROS in atherosclerosis progression, the failure of antioxidant therapy in human randomized clinical trials1-3 demands more definitive, cell-type specific investigations. Better mechanistic understanding of mtROS in atherosclerosis may lead to more effective therapeutic strategies.

show abstract

Role of mitochondrial DNA variants and copy number in diabetic atherogenesis

Cited by 20 publications

References 25 publications

Expression of high-mobility group box protein 1 in diabetic foot atherogenesis

Expression of high-mobility group box protein 1 in diabetic foot atherogenesis

Tissue-specific mtDNA abundance from exome data and its correlation with mitochondrial transcription, mass and respiratory activity

Emerging Roles of Mitochondria ROS in Atherosclerotic Lesions: Causation or Association?

Contact Info

Product

Resources

About