title: Changes of mitochondria in atherosclerosis: possible determinant in the pathogenesis of the disease.
abstract: Electron-microscopic analysis of atherosclerotic lesions demonstrated a high variability in the ultrastructural appearance of mitochondria in human aortic atherosclerotic lesions compared with the appearance of mitochondria in the normal parts of the aortic intima. This prompted us to suggest that the structural variations in the appearance of mitochondria might reflect the existence of somatic mutations in the human mitochondrial genome which could be a determinant of atherosclerosis. To test this hypothesis, we have compared the levels of heteroplasmy for several mitochondrial mutations previously proposed to be associated with different types of atherosclerotic lesions. The homogenates of unaffected aortic intimae and lipofibrous plaques of 12 male aortas were compared to reveal the average level of heteroplasmy for A1555G, C3256T, T3336T, G12315A, G14459A, and G15059A mutations of human mitochondrial genome. It has been shown at least four mutations of mitochondrial genome, namely, A1555G in MT-RNR1 gene, C3256T in MT-TL1 gene, G12315A in MT-TL2 gene, and G15059A in MT-CYB gene have significantly higher prevalence and mean value in lipofibrous plaques as compared to non-atherosclerotic intima, and therefore are associated with atherosclerosis. Somatic mutations in the human mitochondrial genome might play a role in the development of atherosclerosis. The mitochondrial mutations observed in our study should encourage further exploration of the concept that mitochondrial DNA heteroplasmy might be used as a biomarker of atherogenesis.
authors: Russian Cardiology Research and Production Complex, 121552 Moscow, Russia.
authors: Igor A
authors: IA
authors: Sobenin
authors: Margarita A
authors: MA
authors: Sazonova
authors: Anton Y
authors: AY
authors: Postnov
authors: Yuri V
authors: YV
authors: Bobryshev
authors: Alexander N
authors: AN
authors: Orekhov
mesh_terms: D000368:Aged; D001011:Aorta / Q000473:pathology; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology*; D017931:DNA Primers / Q000235:genetics; D004272:DNA, Mitochondrial / Q000378:metabolism; D050259:Genes, Mitochondrial; D006801:Humans; D008297:Male; D008854:Microscopy, Electron / Q000379:methods; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D009154:Mutation; D017539:Tunica Intima / Q000473:pathology
chemical_list: D017931:DNA Primers; D004272:DNA, Mitochondrial