PMID- 32075646
OWN - NLM
STAT- MEDLINE
DCOM- 20200831
LR  - 20200831
IS  - 1475-2840 (Electronic)
IS  - 1475-2840 (Linking)
VI  - 19
IP  - 1
DP  - 2020 Feb 19
TI  - Mitochondrial 8-hydroxy-2'-deoxyguanosine and coronary artery disease in patients 
      with type 2 diabetes mellitus.
PG  - 22
LID - 10.1186/s12933-020-00998-6 [doi]
LID - 22
AB  - BACKGROUND: Little is known about whether mitochondria 
      8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of mitochondrial DNA (mtDNA) 
      oxidative damage, contributes to the development of coronary artery disease (CAD) 
      in diabetic patients. Here, we explored the associations of mtDNA 8-OHdG in 
      leukocytes with obstructive CAD, coronary stenosis severity, cardiovascular 
      biomarkers, and 1-year adverse outcomes after coronary revascularization in 
      patients with type 2 diabetes mellitus (T2DM). METHODS: In a total of 1920 
      consecutive patients with T2DM who underwent coronary angiography due to symptoms 
      of angina or angina equivalents, the presence of obstructive CAD, the number of 
      diseased vessels with >/= 50% stenosis, and modified Gensini score were 
      cross-sectionally evaluated; the level of mtDNA 8-OHdG was quantified by 
      quantitative PCR. Then, 701 of 1920 diabetic patients who further received 
      coronary revascularization completed 1-year prospective follow-up to document 
      major adverse cardiovascular and cerebral events (MACCEs). In vitro experiments 
      were also performed to observe the effects of mtDNA oxidative damage in high 
      glucose-cultured human umbilical vein endothelial cells (HUVECs). RESULTS: 
      Cross-sectionally, greater mtDNA 8-OHdG was associated with increased odds of 
      obstructive CAD (odds ratio [OR] 1.38, 95% CI confidence interval 1.24-1.52), 
      higher degree of coronary stenosis (number of diseased vessels: OR 1.29, 95% CI 
      1.19-1.41; modified Gensini scores: OR 1.28, 95% CI 1.18-1.39), and higher levels 
      of C-reactive protein (beta 0.18, 95% CI 0.06-0.31) after adjusting for confounders. 
      Sensitivity analyses using propensity score matching yielded similar results. 
      Stratification by smoking status showed that the association between mtDNA 8-OHdG 
      and obstructive CAD was most evident in current smokers (P(interation) < 0.01). 
      Prospectively, the adjusted hazards ratio per 1-SD increase in mtDNA 8-OHdG was 
      1.59 (95% CI 1.33-1.90) for predicting 1-year MACCEs after revascularization. In 
      HUVECs, exposure to antimycin A, an inducer for mtDNA oxidative damage, led to 
      adverse alterations in markers of mitochondrial and endothelia function. 
      CONCLUSION: Greater mtDNA 8-OHdG in leukocytes may serve as an independent risk 
      factor for CAD in patients with T2DM.
FAU - Wang, Xue-Bin
AU  - Wang XB
AD  - Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou 
      University, Jianshe East Road No. 1, Zhengzhou, 450000, Henan, China. 
      xbwang2017@163.com.
FAU - Cui, Ning-Hua
AU  - Cui NH
AD  - Zhengzhou Key Laboratory of Children's Infection and Immunity, Children's 
      Hospital Affiliated to Zhengzhou University, Zhengzhou, 450000, Henan, China.
FAU - Liu, Xia'nan
AU  - Liu X
AD  - Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou 
      University, Jianshe East Road No. 1, Zhengzhou, 450000, Henan, China.
FAU - Liu, Xin
AU  - Liu X
AD  - Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou 
      University, Jianshe East Road No. 1, Zhengzhou, 450000, Henan, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200219
PL  - England
TA  - Cardiovasc Diabetol
JT  - Cardiovascular diabetology
JID - 101147637
RN  - 0 (Biomarkers)
RN  - 0 (DNA, Mitochondrial)
RN  - 88847-89-6 (8-Hydroxy-2'-Deoxyguanosine)
SB  - IM
MH  - 8-Hydroxy-2'-Deoxyguanosine/*blood
MH  - Aged
MH  - Biomarkers/blood
MH  - Cells, Cultured
MH  - China/epidemiology
MH  - Coronary Artery Disease/*blood/diagnostic imaging/epidemiology/therapy
MH  - Coronary Stenosis/*blood/diagnostic imaging/epidemiology/therapy
MH  - Cross-Sectional Studies
MH  - *DNA Damage
MH  - DNA, Mitochondrial/*blood
MH  - Diabetes Mellitus, Type 2/*blood/diagnosis/epidemiology
MH  - Female
MH  - Human Umbilical Vein Endothelial Cells/metabolism
MH  - Humans
MH  - Leukocytes/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Myocardial Revascularization/adverse effects
MH  - Oxidative Stress
MH  - Prospective Studies
MH  - Risk Assessment
MH  - Risk Factors
MH  - Severity of Illness Index
MH  - Time Factors
MH  - Treatment Outcome
PMC - PMC7029479
OTO - NOTNLM
OT  - Clinical outcomes after revascularization
OT  - Coronary artery disease
OT  - Mitochondrial 8-OHdG
OT  - Type 2 diabetes mellitus
COIS- The authors declare that they have no competing interests.
EDAT- 2020/02/23 06:00
MHDA- 2020/09/01 06:00
PMCR- 2020/02/19
CRDT- 2020/02/21 06:00
PHST- 2019/12/27 00:00 [received]
PHST- 2020/02/06 00:00 [accepted]
PHST- 2020/02/21 06:00 [entrez]
PHST- 2020/02/23 06:00 [pubmed]
PHST- 2020/09/01 06:00 [medline]
PHST- 2020/02/19 00:00 [pmc-release]
AID - 10.1186/s12933-020-00998-6 [pii]
AID - 998 [pii]
AID - 10.1186/s12933-020-00998-6 [doi]
PST - epublish
SO  - Cardiovasc Diabetol. 2020 Feb 19;19(1):22. doi: 10.1186/s12933-020-00998-6.