人类主动脉动脉粥样硬化病变中线粒体遗传变异的镶嵌性。
Mosaicism of mitochondrial genetic variation in atherosclerotic lesions of the human aorta.
作者信息
Sazonova Margarita A, Sinyov Vasily V, Barinova Valeria A, Ryzhkova Anastasia I, Zhelankin Andrey V, Postnov Anton Y, Sobenin Igor A, Bobryshev Yuri V, Orekhov Alexander N
机构信息
Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 8 Baltiyskaya Street, Moscow 125315, Russia ; Laboratory of Medical Genetics, Russian Cardiology Research and Production Complex, 15a 3rd Cherepkovskaya Street, Moscow 121552, Russia.
Laboratory of Medical Genetics, Russian Cardiology Research and Production Complex, 15a 3rd Cherepkovskaya Street, Moscow 121552, Russia.
出版信息
Biomed Res Int. 2015;2015:825468. doi: 10.1155/2015/825468. Epub 2015 Mar 5.
OBJECTIVE
The aim of the present study was an analysis of heteroplasmy level in mitochondrial mutations 652delG, A1555G, C3256T, T3336C, 652insG, C5178A, G12315A, G13513A, G14459A, G14846A, and G15059A in normal and affected by atherosclerosis segments of morphologically mapped aortic walls.
METHODS
We investigated the 265 normal and atherosclerotic tissue sections of 5 human aortas. Intima of every aorta was divided according to morphological characteristics into segments with different types of atherosclerotic lesions: fibrous plaque, lipofibrous plaque, primary atherosclerotic lesion (fatty streak and fatty infiltration), and normal intima from human aorta. PCR-fragments were analyzed by a new original method developed in our laboratory on the basis of pyrosequence technology.
RESULTS
According to the obtained data, mutations G12315A and G14459A are significantly associated with total and primary atherosclerotic lesions of intimal segments and lipofibrous plaques (P ≤ 0.01 and P ≤ 0.05, accordingly). Mutation C5178A is significantly associated with fibrous plaques and total atherosclerotic lesions (P ≤ 0.01). A1555G mutation shows an antiatherosclerotic effect in primary lesion in lipofibrous plaques (P ≤ 0.05). Meanwhile, G14846A mutation is antiatherogenic for lipofibrous plaques (P ≤ 0.05).
CONCLUSION
Therefore, mutations C5178A, G14459A, G12315A, A1555G, and G14846A were found to be associated with atherosclerotic lesions.
目的
本研究旨在分析线粒体突变652delG、A1555G、C3256T、T3336C、652insG、C5178A、G12315A、G13513A、G14459A、G14846A和G15059A在形态学定位的主动脉壁正常及动脉粥样硬化病变节段中的异质性水平。
方法
我们研究了5例人体主动脉的265个正常和动脉粥样硬化组织切片。根据形态学特征，将每个主动脉的内膜分为不同类型动脉粥样硬化病变的节段：纤维斑块、脂质纤维斑块、原发性动脉粥样硬化病变（脂纹和脂肪浸润）以及来自人体主动脉的正常内膜。采用我们实验室基于焦磷酸测序技术开发的一种新的原创方法分析PCR片段。
结果
根据所得数据，突变G12315A和G14459A与内膜节段的总动脉粥样硬化病变和原发性动脉粥样硬化病变以及脂质纤维斑块显著相关（相应地，P≤0.01和P≤0.05）。突变C5178A与纤维斑块和总动脉粥样硬化病变显著相关（P≤0.01）。A1555G突变在脂质纤维斑块的原发性病变中显示出抗动脉粥样硬化作用（P≤0.05）。同时，G14846A突变对脂质纤维斑块具有抗动脉粥样硬化作用（P≤0.05）。
结论
因此，发现突变C5178A、G14459A、G12315A、A1555G和G14846A与动脉粥样硬化病变相关。
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