Heteroplasmic Variants of Mitochondrial DNA in Atherosclerotic Lesions of Human Aortic Intima
Mitochondrial dysfunction and oxidative stress are likely involved in atherogenesis. Since the mitochondrial genome variation can alter functional activity of cells, it is necessary to assess the presence in atherosclerotic lesions of mitochondrial DNA (mtDNA) heteroplasmic mutations known to be ass...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-09-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/9/9/455 |
| _version_ | 1818048057464324096 |
|---|---|
| author | Igor A. Sobenin Andrey V. Zhelankin Zukhra B. Khasanova Vasily V. Sinyov Lyudmila V. Medvedeva Maria O. Sagaidak Vsevolod J. Makeev Kira I. Kolmychkova Anna S. Smirnova Vasily N. Sukhorukov Anton Y. Postnov Andrey V. Grechko Alexander N. Orekhov |
| author_facet | Igor A. Sobenin Andrey V. Zhelankin Zukhra B. Khasanova Vasily V. Sinyov Lyudmila V. Medvedeva Maria O. Sagaidak Vsevolod J. Makeev Kira I. Kolmychkova Anna S. Smirnova Vasily N. Sukhorukov Anton Y. Postnov Andrey V. Grechko Alexander N. Orekhov |
| author_sort | Igor A. Sobenin |
| collection | DOAJ |
| description | Mitochondrial dysfunction and oxidative stress are likely involved in atherogenesis. Since the mitochondrial genome variation can alter functional activity of cells, it is necessary to assess the presence in atherosclerotic lesions of mitochondrial DNA (mtDNA) heteroplasmic mutations known to be associated with different pathological processes and ageing. In this study, mtDNA heteroplasmy and copy number (mtCN) were evaluated in the autopsy-derived samples of aortic intima differing by the type of atherosclerotic lesions. To detect mtDNA heteroplasmic variants, next generation sequencing was used, and mtCN measurement was performed by qPCR. It was shown that mtDNA heteroplasmic mutations are characteristic for particular areas of intimal tissue; in 83 intimal samples 55 heteroplasmic variants were found; mean minor allele frequencies level accounted for 0.09, with 12% mean heteroplasmy level. The mtCN variance measured in adjacent areas of intima was high, but atherosclerotic lesions and unaffected intima did not differ significantly in mtCN values. Basing on the ratio of minor and major nucleotide mtDNA variants, we can conclude that there exists the increase in the number of heteroplasmic mtDNA variants, which corresponds to the extent of atherosclerotic morphologic phenotype. |
| first_indexed | 2024-12-10T10:15:38Z |
| format | Article |
| id | doaj.art-32cb36e78d2b40fc83c0adc4d72dba0d |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-12-10T10:15:38Z |
| publishDate | 2019-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-32cb36e78d2b40fc83c0adc4d72dba0d2022-12-22T01:53:00ZengMDPI AGBiomolecules2218-273X2019-09-019945510.3390/biom9090455biom9090455Heteroplasmic Variants of Mitochondrial DNA in Atherosclerotic Lesions of Human Aortic IntimaIgor A. Sobenin0Andrey V. Zhelankin1Zukhra B. Khasanova2Vasily V. Sinyov3Lyudmila V. Medvedeva4Maria O. Sagaidak5Vsevolod J. Makeev6Kira I. Kolmychkova7Anna S. Smirnova8Vasily N. Sukhorukov9Anton Y. Postnov10Andrey V. Grechko11Alexander N. Orekhov12Institute of Experimental Cardiology, National Medical Research Center of Cardiology, 121552 Moscow, RussiaFederal Research and Clinical Center of Physical-Chemical Medicine, 119435 Moscow, RussiaInstitute of Experimental Cardiology, National Medical Research Center of Cardiology, 121552 Moscow, RussiaInstitute of Experimental Cardiology, National Medical Research Center of Cardiology, 121552 Moscow, RussiaFederal Research Center of Transplantology and Artificial Organs, 123182 Moscow, RussiaVavilov Institute of General Genetics, 117971 Moscow, RussiaVavilov Institute of General Genetics, 117971 Moscow, RussiaInstitute for Atherosclerosis Research, Skolkovo Innovation Center, 143026 Moscow, RussiaInstitute for Atherosclerosis Research, Skolkovo Innovation Center, 143026 Moscow, RussiaInstitute of Experimental Cardiology, National Medical Research Center of Cardiology, 121552 Moscow, RussiaInstitute of Experimental Cardiology, National Medical Research Center of Cardiology, 121552 Moscow, RussiaFederal Scientific Clinical Center for Resuscitation and Rehabilitation, 141534 Moscow Region, RussiaInstitute for Atherosclerosis Research, Skolkovo Innovation Center, 143026 Moscow, RussiaMitochondrial dysfunction and oxidative stress are likely involved in atherogenesis. Since the mitochondrial genome variation can alter functional activity of cells, it is necessary to assess the presence in atherosclerotic lesions of mitochondrial DNA (mtDNA) heteroplasmic mutations known to be associated with different pathological processes and ageing. In this study, mtDNA heteroplasmy and copy number (mtCN) were evaluated in the autopsy-derived samples of aortic intima differing by the type of atherosclerotic lesions. To detect mtDNA heteroplasmic variants, next generation sequencing was used, and mtCN measurement was performed by qPCR. It was shown that mtDNA heteroplasmic mutations are characteristic for particular areas of intimal tissue; in 83 intimal samples 55 heteroplasmic variants were found; mean minor allele frequencies level accounted for 0.09, with 12% mean heteroplasmy level. The mtCN variance measured in adjacent areas of intima was high, but atherosclerotic lesions and unaffected intima did not differ significantly in mtCN values. Basing on the ratio of minor and major nucleotide mtDNA variants, we can conclude that there exists the increase in the number of heteroplasmic mtDNA variants, which corresponds to the extent of atherosclerotic morphologic phenotype.https://www.mdpi.com/2218-273X/9/9/455atherosclerosismitochondrial DNA mutationsnext generation sequencingmitochondrial DNA copy numberunaffected intimafatty infiltrationfatty streakslipofibrous plaquefibrous plaque |
| spellingShingle | Igor A. Sobenin Andrey V. Zhelankin Zukhra B. Khasanova Vasily V. Sinyov Lyudmila V. Medvedeva Maria O. Sagaidak Vsevolod J. Makeev Kira I. Kolmychkova Anna S. Smirnova Vasily N. Sukhorukov Anton Y. Postnov Andrey V. Grechko Alexander N. Orekhov Heteroplasmic Variants of Mitochondrial DNA in Atherosclerotic Lesions of Human Aortic Intima Biomolecules atherosclerosis mitochondrial DNA mutations next generation sequencing mitochondrial DNA copy number unaffected intima fatty infiltration fatty streaks lipofibrous plaque fibrous plaque |
| title | Heteroplasmic Variants of Mitochondrial DNA in Atherosclerotic Lesions of Human Aortic Intima |
| title_full | Heteroplasmic Variants of Mitochondrial DNA in Atherosclerotic Lesions of Human Aortic Intima |
| title_fullStr | Heteroplasmic Variants of Mitochondrial DNA in Atherosclerotic Lesions of Human Aortic Intima |
| title_full_unstemmed | Heteroplasmic Variants of Mitochondrial DNA in Atherosclerotic Lesions of Human Aortic Intima |
| title_short | Heteroplasmic Variants of Mitochondrial DNA in Atherosclerotic Lesions of Human Aortic Intima |
| title_sort | heteroplasmic variants of mitochondrial dna in atherosclerotic lesions of human aortic intima |
| topic | atherosclerosis mitochondrial DNA mutations next generation sequencing mitochondrial DNA copy number unaffected intima fatty infiltration fatty streaks lipofibrous plaque fibrous plaque |
| url | https://www.mdpi.com/2218-273X/9/9/455 |
| work_keys_str_mv | AT igorasobenin heteroplasmicvariantsofmitochondrialdnainatheroscleroticlesionsofhumanaorticintima AT andreyvzhelankin heteroplasmicvariantsofmitochondrialdnainatheroscleroticlesionsofhumanaorticintima AT zukhrabkhasanova heteroplasmicvariantsofmitochondrialdnainatheroscleroticlesionsofhumanaorticintima AT vasilyvsinyov heteroplasmicvariantsofmitochondrialdnainatheroscleroticlesionsofhumanaorticintima AT lyudmilavmedvedeva heteroplasmicvariantsofmitochondrialdnainatheroscleroticlesionsofhumanaorticintima AT mariaosagaidak heteroplasmicvariantsofmitochondrialdnainatheroscleroticlesionsofhumanaorticintima AT vsevolodjmakeev heteroplasmicvariantsofmitochondrialdnainatheroscleroticlesionsofhumanaorticintima AT kiraikolmychkova heteroplasmicvariantsofmitochondrialdnainatheroscleroticlesionsofhumanaorticintima AT annassmirnova heteroplasmicvariantsofmitochondrialdnainatheroscleroticlesionsofhumanaorticintima AT vasilynsukhorukov heteroplasmicvariantsofmitochondrialdnainatheroscleroticlesionsofhumanaorticintima AT antonypostnov heteroplasmicvariantsofmitochondrialdnainatheroscleroticlesionsofhumanaorticintima AT andreyvgrechko heteroplasmicvariantsofmitochondrialdnainatheroscleroticlesionsofhumanaorticintima AT alexandernorekhov heteroplasmicvariantsofmitochondrialdnainatheroscleroticlesionsofhumanaorticintima |