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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Wang, Xue-bin Cui, Ning-hua Liu, Xia’nan Liu, Xin |
| Abstract | 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 (β 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 (Pinteration < 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. |
| Related Links | https://cardiab.biomedcentral.com/counter/pdf/10.1186/s12933-020-00998-6.pdf |
| Ending Page | 15 |
| Page Count | 15 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 14752840 |
| DOI | 10.1186/s12933-020-00998-6 |
| Journal | Cardiovascular Diabetology |
| Issue Number | 1 |
| Volume Number | 19 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2020-02-19 |
| Access Restriction | Open |
| Subject Keyword | Diabetes Angiology Cardiology Mitochondrial 8-OHdG Coronary artery disease Type 2 diabetes mellitus Clinical outcomes after revascularization |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cardiology and Cardiovascular Medicine Internal Medicine Endocrinology, Diabetes and Metabolism |
| Journal Impact Factor | 8.5/2023 |
| 5-Year Journal Impact Factor | 8.9/2023 |
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