Mosaicism of Mitochondrial Genetic Variation in Atherosclerotic Lesions of the Human Aorta

• Published in: BioMed research international 2015-01, Vol.2015 (2015), p.1-9
• Main Authors: Orekhov, Alexander N., Bobryshev, Yuri V., Postnov, Anton Y., Zhelankin, Andrey V., Ryzhkova, Anastasia I., Barinova, Valeria A., Sinyov, Vasily V., Sazonova, Margarita A., Sobenin, Igor A.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aorta; Aorta - pathology; Atherosclerosis; Atherosclerosis - genetics; Atherosclerosis - pathology; Biomedical research; Extracellular matrix; Female; Genetic aspects; Genetic Association Studies; Genetic variation; Genome, Mitochondrial - genetics; Genomes; Health aspects; Humans; Laboratories; Lipids; Male; Middle Aged; Mitochondria - genetics; Mitochondrial DNA; Morphology; Mortality; Mosaicism; Mutation; Mutation - genetics; Observations; Pathology; Physiological aspects; Plaque, Atherosclerotic - genetics; Plaque, Atherosclerotic - pathology; Studies; Tunica Intima - pathology
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2015/825468

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.