Preview

Клиницист

Расширенный поиск

Возможная роль мутаций митохондриального генома при ишемической болезни сердца

https://doi.org/10.17650/1818-8338-2013-2-6-13

Полный текст:

Аннотация

Митохондрии являются не только основными производителями аденозинтрифосфата, но и эндогенным источником активных форм кислорода. Митохондриальная дисфункция играет ключевую роль в запуске и прогрессировании атеросклеротического поражения. Нарушение функций митохондрий вследствие повышения в них уровня окисленных форм кислорода, накопления повреждений митохондриальной ДНК, истощения дыхательных цепей вызывает дисфункцию и апоптоз эндотелиальных клеток, активацию матриксных металлопротеиназ, рост сосудистых гладкомышечных клеток и их миграцию в интиму, экспрессию молекул адгезии и окисление липопротеинов низкой плотности. Митохондриальная дисфункция может быть важным объединяющим механизмом, объясняющим атерогенное действие основных факторов риска сердечно-сосудистых заболеваний. Небольшие клинические пилотные исследования показали ассоциацию различных мутаций митохондриального генома с атеросклеротическим поражением артерий. Учитывая появившиеся данные о возможной роли митохондрий в атерогенезе, в настоящее время ведутся разработки новых лекарственных препаратов, оказывающих влияние на функцию митохондрий.

Об авторах

Л. А. Егорова
ФГБУ «Российский кардиологический научно-производственный комплекс» Минздрава России
Россия


М. В. Ежов
ФГБУ «Российский кардиологический научно-производственный комплекс» Минздрава России
Россия


Г. М. Шиганова
ГБУЗ «Городская поликлиника № 2» Департамента здравоохранения г. Москвы
Россия


А. Ю. Постнов
ФГБУ «Российский кардиологический научно-производственный комплекс» Минздрава России
Россия


Список литературы

1. Sobenin I.A., Sazonova M.A., Ivanova M.M. et al. Mutation C3256T of mitochondrial genome in white blood cells: novel genetic marker of atherosclerosis and coronary heart disease. PLoS One 2012;7(10):46573.

2. Anderson S., Bankier A.T., Barrell B.G. et al. Sequence and organization of the human mitochondrial genome. Nature 1981;290(5806):457–65.

3. Camara A.K., Lesnefsky E.J., Stowe D.F. Potential therapeutic benefits of stretegies directed to mitochondria. Antioxid Redox Signal 2010;13(3):279–347.

4. Lenka N., Vijayasarathy C., Mullick J., Avadhani N.G. Structural organization and transcription regulation of nuclear genes encoding the mammalian cytochrome c oxidase complex. Prog Nucleic Acid Res Mol Biol 1998;61:309–44.

5. Ballinger S.W., Petterson C., Yan C.N. et al. Hydrogen peroxide- and peroxynitriteinduced mitochondrial DNA damage and dysfunction in vascular endothelial and smooth muscle cells. Circ Res 2000;86(9):960–6.

6. Тодоров И.Н., Тодоров Г.И. Мультифакторная природа высокой частоты мутаций в мтДНК cоматических клеток млекопитающих. Биохимия 2009;74(9):1184–94.

7. Wallace D.C., Ye J.H., Neckelmann S.N. et al. Sequence analysis of cDNAs for the human and bovine ETP synthase beta subunit: mitochondrial DNA genes sustain seventeen times more mutations. Curr Genet 1987;12(2):81–90.

8. Kmiec B., Woloszynska M., Janska H. Heteroplasmy as a common state of mitochondrial genetic information in plants and animals. Curr Genet 2006;50(3):149–59.

9. Wonnapinij P., Chinnery P.F., Samuels D.C. The distribution of mitochondrial DNA heteroplasmy due to random genetic drift. Am J Hum Genet 2008;83(5):582–93.

10. Lightowlers R.N., Chinnery P.F., Turnbull D.M., Howell N. Mammalian mitochondrial genetics: heredity, heteroplasmy and disease. Trends Genet 1997;13(11):450–5.

11. van Blerkom J. Mitochondria as regulatory forces in oocytes, preimplantation embryos and stem cells. Reprod Biomed Online 2008;16(4):553–69.

12. Cree L.M., Samuels D.C., de Sousa Lopes S.C. et al. A reduction of mitochondrial DNA molecules during embryogenesis explains the rapid segregation of genotypes. Net. Genet 2008;40(2):249–54.

13. Lenaz G., Genova M.L. Structure and organization of mitochondrial respiratory complexes: a new understanding of an old subject. Antioxid Redox Signal 2010;12(8):961–1008.

14. Waldmeier P.C. Prospects for antiapoptotic drug therapy of neurodegenerative diseases. Prog

15. Neuropsychopharmacol Biol Psychiatry 2003;27(2):303–21.

16. Fernandez-Moreno M.A., Bornstein В., Petit N., Garesse R. The pathophysiology of mitochondrial

17. biogenesis: towards four decades of mitochondrial DNA research. Mol Genet Metab 2000;71(3):481–95.

18. Dimauro S. Mitochondrial medicine. Biochim Biophys Acta 2004;1659 (2–3):107–14.

19. Irani K. Oxidant signaling in vascular cell growth, death, and survival: a review of the roles of reactive oxygen species in smooth muscle and endothelial cell mitogenic and apoptotic signaling. Circ Res 2000;87(3):179–83.

20. Dedkova E.N., Ji X., Lipsius S.L., Blatter L.A. Mitochondrial calcium uptake stimulates nitric oxide production in mitochondria of bovine vascular endothelial cells. Am J Physiol 2004;286(2):C406–15.

21. Poteser M., Graziani A., Rosker C. et al. TRPC3 and TRPC4 associate to form a redox-sensitive cation channel. Evidence for expression of native TRPC3–TRPC4 heteromeric channels in endothelial cells. J Biol Chem 2006: 281(19):13588–95.

22. Spitaler M.M., Graier W.F. Vascular targets of redox signaling in diabetes mellitus. Diabetologia 2002;45(4):476–94.

23. Knight-Lozano C.A., Young C.G., Burow D.L. et al. Cigarette smoke exposure and hypercholesterolemia increase mitochondrial damage in cardiovascular tissues. Circulation 2002;105(7):849–54.

24. Kelley D.E., He J., Menshikova E.V., Ritov V.B. Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes 2002;51(10):2944–50.

25. Madamanchi N.R., Runge M.S. Mitochondrial dysfunction in atherosclerosis. Circ Res 2007;100(4):460–73.

26. Puddu P., Puddu G.M., Galletti L. et al. Mitochondrial dysfunction as an initiating event in atherogenesis: а plausible hypothesis. Cardiology 2005;103(3):137–41.

27. Dai Y.L., Luk T.H., Siu C.W. et al. Mitochondrial dysfunction induced by statin contributes to endothelial dysfunction in patients with coronary artery disease. Cardiovasc Toxicol 2010;10(2):130–8.

28. Vaux D.L. Apoptogenic factors released from mitochondria. Biochim Biophys Acta 2011;1813(4):546–50.

29. Vindis C., Elbaz M., Escargueil-Blanc I. et al. Two distinct calcium-dependent mitochondrial pathways are involved in oxidized LDL-induced apoptosis. Arterioscler Thromb Vasc Biol 2005:25(3):639–45.

30. Gorenne I., Kavurma M., Scott S., Bennett M. Vascular smooth muscle cell senescence in atherosclerosis. Cardiovasc Res 2006;72(1):9–17.

31. Nakamura N., Hattori N., Tanaka M., Mizuno Y. Specific detection of deleted mitochondrial DNA by in situ hybridization using a chimera probe. Biochim Biophys Acta 1996;1308(3):215–21.

32. Botto N., Rizza A., Colombo M.G. et al. Evidence for DNA damage in patients with coronary artery disease. Mutat Res 2001;493(1–2):23–30.

33. Martinet W., Knaapen M.W., De Meyer G.R. et al. Elevated levels of oxidative DNA damage and DNA repair enzymes in human atherosclerotic plaques. Circulation 2002;20;106(8):927–32.

34. Ballinger S.W., Patterson C., Knight Lozano C.A. et al. Mitochondrial integrity and function in atherogenesis. Circulation 2002;106(5):544–9.

35. Ballinger S.W. Mitochondrial dysfunction in cardiovascular disease. Free Radic Biol Med 2005;38(10):1278–95.

36. Harrison D., Griendling K.K., Landmesser U. et al. Role of oxidative stress in atherosclerosis. Am J Cardiol 2003;91(3A):7A–11A.

37. Fearon I.M., Faux S.P. Oxidative stress and cardiovascular disease: novel tools give (free) radical insight. J Mol Cell Cardiol 2009;47(3):372–81.

38. Yao P.M., Tabas I. Free cholesterol loading of macrophages is associeted with widespread mitochondrial dysfunction and activation of the mitochondrial apoptosis pathway. J Biol Chem 2001;276(45):42468–76.

39. Raha S., Robinson B.H. Mitochondria, oxygen free radicals, and apoptosis. Am J Med Genet 2001;106(1):62–70.

40. Fleming I., Mohamed A., Galle J. et al. Oxidized low-density lipoprotein increases superoxide production by endothelial nitric oxide synthase by inhibiting PKCalpha. Cardiovasc Res 2005;65(4):897–906.

41. Geng Y.J., Libby P. Progression of atheroma: a struggle between death and procreation. Arterioscler Thromb Vasc Biol 2002;22(9):1370–80.

42. Ward N.C., Croft K.D. Hypertension and oxidative stress. Clin Exp Pharmacol Physiol 2006;33(9):872–6.

43. Postnov Iu.V. The role of mitochondrial calcium overload and energy deficiency in pathogenesis of arterial hypertension. Arkh Patol 2001;63(3):3–10.

44. Miró O., Alonso J.R., Jarreta D.et al. Smoking disturbs mitochondrial respiratory chain function and enhances lipid peroxidation on human circulating lymphocytes. Carcinogenesis 1999;20(7):1331–6.

45. Andreassi M.G., Botto N., Colombo M.G. et al. Genetic instability and atherosclerosis: can somatic mutations account for the development of cardiovascular diseases? Environ Mol Mutagen 2000;35(4):265–9.

46. Pohjoismäki J.L., Goffart S., Taylor R.W. et al. Developmental and pathological changes in the human cardiac muscle mitochondrial DNA organization, replication and copy number. PLoS One 2010;5(5):e10426.

47. Rorbach J., Yusoff A.A., Tuppen H. et al. Overexpression of human mitochondrial valyl tRNA synthetase can partially restore levels of cognate mt-tRNAVal carrying the pathogenic C25U mutation. Nucleic Acids Res 2008;36(9):3065–74.

48. Bornstein B., Mas J.A., Patrono C. et al. Comparative analysis of the pathogenic mechanisms associated with the G8363A and A8296G mutations in the mitochondrial tRNA(Lys) gene. Biochem J 2005;387(Pt3):773–8.

49. Raha S., Merante F., Shoubridge E. et al. Repopulation of rho0 cells with mitochondria from a patient with a mitochondrial DNA point mutation in tRNA(Gly) results in respiratory chain dysfunction. Hum Mutat 1999;13(3):245–54.

50. Mimaki M., Ikota A., Seto A. et al. A double mutation (G11778A and G12192A) in mitochondrial DNA associated with Leber's hereditary optic neuropathy and cardiomyopathy. J Hum Genet 2003;48(1):47–50.

51. Chol M., Lebon S., Bénit P. et al. The mitochondrial DNA G13513A MELAS mutetion in the NADH dehydrogenase 5 gene is a frequent cause of Leigh-like syndrome with isolated complex I deficiency. J Med Genet 2003;40(3):188–91.

52. Sazonova M., Budnikov E., Khasanova Z. et al. Studies of human aortic intima by a direct quantitative assay of mutant alleles in the mitochondrial genome. Atherosclerosis 2009;204(1):184–90.

53. Moraes C.T., Ciacci F., Bonilla E. et al. Two novel pathogenic mitochondrial DNA mutations affecting organelle number and protein synthesis. Is the tRNA(Leu(UUR)) gene an etiologic hot spot? J Clin Invest 1993;92(2):2906–15.

54. Rossmanith W., Karwan R.M. Impairment of tRNA processing by point mutations in mitochondrial tRNA(Leu) (UUR) associated with mitochondrial diseases. FEBS Lett 1998;433(3):269–74.

55. Mueller E.E., Eder W., Ebner S. et al. The mitochondrial T16189C polymorphism is associated with coronary artery disease in Middle European populations. PLoS One 2011;6(1):e16455.

56. Piot C., Croisille P., Staat P. et al. Effect of cyclosporine on reperfusion injury in acute myocardial infarction. N Engl J Med 2008;359(5):473–81.

57. Mewton N., Croisille P., Gahide G. et al. Effect of cyclosporine on left ventricular remodeling after reperfused myocardial infarction. J Am Coll Cardiol 2010;55(12):1200–5.

58. Rudolph V., Rudolph T.K., Schopfer F.J. et al. Endogenous generation and protective effects of nitro-fatty acids in a murine model of focal cardiac ischaemia and reperfusion. Cardiovasc Res 2010;85(1):155–66.

59. Shiva S., Sack M.N., Greer J.J. et al. Nitrite augments tolerance to ischemia/reperfusion injury via the modulation of mitochondrial electron transfer. J Exp Med 2007;204(9):2089–102.

60. Mureta M., Akao M., O’Rourke B., Marbоn E. Mitochondrial ETP-sensitive potassium channels attenuate matrix Ca(2+) overload during simulated ischemia and reperfusion: possible mechanism of

61. cardioprotection. Circ Res 2001;89(10):891–8.

62. Deja M.A., Malinowski M., Golba K.S. et al. Diazoxide protects myocardial mitochondria, metabolism, and function during cardiac surgery: a double-blind randomized feasibility study of diazoxidesupplemented cardioplegia. J Thorac Cardiovasc Surg 2009;137(4):997–1004.

63. Yusuf S., Dagenais G., Pogue J. et al. Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000;342(3):154–60.

64. Victor V.M., Rocha M., De la Fuente M. N-acetylcysteine protects mice from lethal endotoxemia by regulating the redox state of immune cells. Free Radic Res 2003;37(9):919–29.

65. Victor V.M., Rocha M., Esplugues J.V., De la Fuente M. Role of free radicals in sepsis: antioxidant therapy. Curr Pharm Des 2005;11(24):3141–58.

66. Armstrong J.S. Mitochondrial medicine: pharmacological targeting of mitochondria in disease. Br J Pharmacol 2007;151(8):1154–65.

67. Luk T.H., Dai Y.L., Siu C.W. et al. Habitual physical activity is associated with endothelial function and endothelial progenitor cells in patients with stable coronary artery disease. Eur J Cardiovasc Prev Rehabil 2009;16(4):464–71.


Для цитирования:


Егорова Л.А., Ежов М.В., Шиганова Г.М., Постнов А.Ю. Возможная роль мутаций митохондриального генома при ишемической болезни сердца. Клиницист. 2013;7(2):6-13. https://doi.org/10.17650/1818-8338-2013-2-6-13

For citation:


Egorova L.A., Ezhov M.V., Shiganova G.M., Postnov A.Y. POSSIBLE ROLE OF MITOCHONDRIAL GENOME MUTATIONS IN CORONARY HEART DISEASE. The Clinician. 2013;7(2):6-13. (In Russ.) https://doi.org/10.17650/1818-8338-2013-2-6-13

Просмотров: 379


Creative Commons License
Контент доступен под лицензией Creative Commons Attribution 4.0 License.


ISSN 1818-8338 (Print)
ISSN 2412-8775 (Online)