Abstract
Somatic mutations of the human mitochondrial genome can be a possible determinant of atherosclerosis. To test this possibility, forty mitochondrial mutations were analyzed in the present study in order to see which of these mutations might be associated with atherosclerosis. Ten mitochondrial mutations belonging to mitochondrial genes MT-RNR1 (rRNA 12S); MT-TL1 (tRNA-Leu, recognizes UUR); MT-TL2 (tRNA-Leu, recognizes CUN); MT-ND1, MT-ND2, MT-ND5, and MT-ND6 (subunits 1, 2, 5, and 6, respectively, of NADH dehydrogenase); and MT-CYB (cytochrome b) were potentially associated with atherosclerosis. From 29% (2 of 7 aortic samples) upto 86% (6 of 7 aortic samples) of aortic samples had a significant difference between atherosclerotic plaques and unaffected tissue, with the respect to the level of heteroplasmy for each mutation. Further, the homogenates of affected and normal intimae of 22 aortas were compared to reveal the average level of heteroplasmy for the above-mentioned 10 mutations. For five mutations, the mean level of heteroplasmy was significantly different in atherosclerotic intimal homogenates in comparison with the unaffected tissue. These mutations were A1555G, C3256T, T3336C, G13513A, and G15059A. Thus, it was demonstrated that at least five mitochondrial mutations occurring in MT-RNR1, MT-TL1, MT-ND2, MT-ND5, and MT-CYB genes are associated with atherosclerosis.
Highlights
Atherosclerosis underlies the development of most cardiovascular diseases, which are the leading cause of death in the 21st century
Ten mitochondrial mutations belonging to mitochondrial genes MT-RNR1; MT-TL1; MT-TL2; MT-ND1, MT-ND2, MT-ND5, and MT-ND6; and MT-CYB were potentially associated with atherosclerosis
It was demonstrated that at least five mitochondrial mutations occurring in MT-RNR1, MT-TL1, MT-ND2, MT-ND5, and MT-CYB genes are associated with atherosclerosis
Summary
Atherosclerosis underlies the development of most cardiovascular diseases, which are the leading cause of death in the 21st century. The mechanisms involved in the development of atherosclerosis have been intensively studied and various mechanisms and factors responsible for atherosclerotic alteration of the arterial intima have been suggested. We suggested that somatic mutations within the mitochondrial genome may be a probable cause of atherosclerosis development in humans [5]. The mitochondrial DNA (mtDNA) spans 16,569 DNA base pairs and is represented by a two-stranded circular molecule containing 37 genes. The two strands of mtDNA are differentiated by their nucleotide content, with the guaninerich strand referred to as the heavy strand, and the cytosinerich strand referred to as the light strand. The subunits of complexes of a respiratory chain (cytochrome b, ATP synthase, cytochrome c oxidase, and NADH dehydrogenase) are encoded with mtDNA. Mitochondrial DNA is susceptible to reactive oxygen species generated by the respiratory chain due to their
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