Kirichenko Tatiana V, Ryzhkova Anastasia I, Sinyov Vasily V, Sazonova Marina D, Orekhova Varvara A, Karagodin Vasily P, Gerasimova Elena V, Voevoda Mikhail I, Orekhov Alexander N, Ragino Yulia I, Sobenin Igor A, Sazonova Margarita A
Laboratory of Cellular and Molecular Pathology of Cardiovascular System, Research Institute of Human Morphology, 3 Tsyurupy Str., 117418 Moscow, Russia.
Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 8 Baltiyskaya Str., 125315 Moscow, Russia.
Life (Basel). 2020 Aug 22;10(9):160. doi: 10.3390/life10090160.
The search for markers of predisposition to atherosclerosis development is very important for early identification of individuals with a high risk of cardiovascular disease. The aim of the present study was to investigate the association of mitochondrial DNA mutations with carotid intima-media thickness and to determine the impact of mitochondrial heteroplasmy measurements in the prognosis of atherosclerosis development. This cross-sectional, population-based study was conducted in 468 subjects from the Novosibirsk region. It was shown that the mean (carotid intima-media thickness) cIMT correlated with the following mtDNA mutations: m.15059G>A ( = 0.159, = 0.001), m.12315G>A ( = 0.119; = 0.011), m.5178C>A ( = 0.114, = 0.014), and m.3256C>T ( = 0.130, = 0.011); a negative correlation with mtDNA mutations m.14846G>A ( = -0.111, = 0.042) and m.13513G>A ( = -0.133, = 0.004) was observed. In the linear regression analysis, the addition of the set of mtDNA mutations to the conventional cardiovascular risk factors increased the ability to predict the cIMT variability from 17 to 27%. Multi-step linear regression analysis revealed the most important predictors of mean cIMT variability: age, systolic blood pressure, blood levels of total cholesterol, LDL and triglycerides, as well as the mtDNA mutations m.13513G>A, m.15059G>A, m.12315G>A, and m.3256C>T. Thus, a high predictive value of mtDNA mutations for cIMT variability was demonstrated. The association of mutation m.13513G>A and m.14846G>A with a low value of cIMT, demonstrated in several studies, represents a potential for the development of anti-atherosclerotic gene therapy.
寻找动脉粥样硬化发展易感性的标志物对于早期识别心血管疾病高危个体非常重要。本研究的目的是调查线粒体DNA突变与颈动脉内膜中层厚度的关联，并确定线粒体异质性测量对动脉粥样硬化发展预后的影响。这项基于人群的横断面研究在新西伯利亚地区的468名受试者中进行。结果显示，平均（颈动脉内膜中层厚度）cIMT与以下线粒体DNA突变相关：m.15059G>A（r = 0.159，p = 0.001）、m.12315G>A（r = 0.119；p = 0.011）、m.5178C>A（r = 0.114，p = 0.014）和m.3256C>T（r = 0.130，p = 0.011）；观察到与线粒体DNA突变m.14846G>A（r = -0.111，p = 0.042）和m.13513G>A（r = -0.133，p = 0.004）呈负相关。在线性回归分析中，将线粒体DNA突变集添加到传统心血管危险因素中，可将预测cIMT变异性的能力从17%提高到27%。多步线性回归分析揭示了平均cIMT变异性的最重要预测因素：年龄、收缩压、总胆固醇、低密度脂蛋白和甘油三酯的血液水平，以及线粒体DNA突变m.13513G>A、m.15059G>A、m.12315G>A和m.3256C>T。因此，证明了线粒体DNA突变对cIMT变异性具有较高的预测价值。几项研究中显示的突变m.13513G>A和m.14846G>A与低cIMT值的关联代表了抗动脉粥样硬化基因治疗发展的潜力。
