Статья
Инфекционные агенты в развитии атеросклероза
К началу 21-го века существует более 25 гипотез и «теорий» атеросклероза, 240 факторов, способствующих возникновению атеросклеротических изменений сосудистой стенки. В последние годы все больше авторов склоняются к точке зрения, что атеросклероз представляет собой хронический иммуновоспалительный процесс, который протекает по типу реакции гиперчувствительности замедленного типа. Причиной воспалительной реакции как во времядекомпенсации хронической сосудисто-мозговой недостаточности, так и при атеросклерозе вообще может быть персистирующая инфекция брахиоцефальных, церебральных и коронарных артерий. Изучены и проанализированы зарубежные исследования по определению роли инфекционных агентов в развитии атеросклеротических изменений сосудистой стенки. Выявлено, что различные инфекционные агенты могут быть задействованы в развитии атеросклероза как по отдельности, так и в комплексе. Бактерии и вирусы могут участвовать в процессах формирования и дестабилизации атеросклеротических бляшек, приводить к повреждению эндотелия, запускать в нем системные иммунные реакции и коагуляционные механизмы, индуцировать клеточную инфильтрацию и выработку провоспалительных факторов. На сегодняшний день не существует единого мнения о том, является ли роль инфекционных патогенов в атеросклеротическом воспалении первичной либо они потенцируют уже начавшийся процесс.
1. Department of Health Statistics and Informatics World Health Organization, Geneva April 2011. Causes of death 2008: data sources and methods Available from: URL: https://kipdf.com/causes-of-death-2008-data-sources-and-methods_5ae5046c7f8b9aa6558b45ab.html
2. Hansson G. K. Inflammation, atherosclerosis, and coronary artery disease // N. Engl. J. Med. 2005. Vol. 352, N 16. P. 1685–1689.
3. Prasad A., Zhu J., Halcox J. P. et al. Predisposition to atherosclerosis by infections: role of endothelial dysfunction // Circulation. 2002. Vol. 106, N 2. P. 184–190.
4. Krebs P., Scandella E., Bolinger B. et al. Chronic immune reactivity against persisting microbial antigen in the vasculature exacerbates atherosclerotic lesion formation // Arterioscler. Thromb. Vasc. Biol. 2007. Vol. 27, N 10. P. 2206–2213.
5. Edfeldt K., Agerberth B., Rottenberg M. E. et al. Involvement of the antimicrobial peptide LL-37 in human atherosclerosis // Arterioscler. Thromb. Vasc. Biol. 2006. Vol. 26, N 7. P. 1551–1557.
6. Плоткин В. Я. Энтеровирусы и функция эндотелия в остром периоде инфаркта миокарда. Сообщение 3 / В. Я. Плоткин [и др.] // Вестн. СПбГУ. Серия 11. Медицина. – 2008. – Вып. 4. – С. 3–12.
7. Kwon T. W., Kim D. K., Ye J. S. et al. Detection of enterovirus, cytomegalovirus, and Chlamydia pneumoniae in atheromas // J. Microbiol. 2004. Vol. 42, N 4. P. 299–304.
8. Kuo H. K., Fujise K. Human papillomavirus and cardiovascular disease among U.S. women in the National Health and Nutrition Examination Survey, 2003 to 2006 // J. Am. Coll. Cardiol. 2011. Vol. 58, N 19. P. 2001–2006.
9. Choi J. I., Chung S. W., Kang H. S. et al. Establishment of Porphyromonas gingivalis heat-shock-proteinspecific T-cell lines from atherosclerosis patients // J. Dent. Res. 2002. Vol. 81, N 5. P. 344–348.
10. Kuo C. C., Jackson L. A., Campbell L. A., Grayston J. T. Chlamydia pneumoniae (TWAR) // Clin. Microbiol. Rev. 1995. Vol. 8, N 4. P. 4. 451–461.
11. Saikku P., Leinonen M., Mattila K. et al. Serological evidence of an association of a novel Chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction // Lancet. 1988. Vol. 2, N 8618. P. 983–986.
12. Godzik K. L., O’Brien E. R., Wangand S. K., Kuo C. C. In vitro susceptibility of human vascular wall cells to infection with Chlamydia pneumoniae // J. Clin. Microbiol. 1995. Vol. 33, N 9. P. 2411–2414.
13. Kalayoglu M. V., Byrne G. I. Induction of macrophage foam cell formation by Chlamydia pneumoniae // J. Infect. Dis. 1998. Vol. 177, N 3. P. 725–729.
14. Glader C. A., Boman J., Saikku P. et al. The pro-atherogenic properties of lipoprotein(a) may be enhanced through the formation of circulating immunecomplexes containing Chlamydia pneumoniae-specific IgG antibodies // Eur. Heart J. 2000. Vol. 21, N 8. P. 639–646.
15. Benagiano M., Azzurri A., Ciervo A. et al. T helper type 1 lymphocytes drive inflammation in human atherosclerotic lesions // Proc. Natl. Acad. Sci. U. S. A. 2003. Vol. 100, N 11. P. 6658–6663.
16. Benagiano M., Munar F., Ciervo A. et al. Chlamydophila pneumoniae phospholipase D (CpPLD) drives Th17 inflammation in human atherosclerosis // Proc. Natl. Acad. Sci. U. S. A. 2012. Vol. 109, N 4. P. 1222–1227.
17. Rödel J., Woytas M., Groh A. et al. Production of basic fibroblast growth factor and interleukin 6 by human smooth muscle cells following infection with Chlamydia pneumoniae // Infect. Immun. 2000. Vol. 68, N 6. P. 3635–3641.
18. Kol A., Sukhova G. K., Lichtman A. H., Libby P. Chlamydial heat shock protein 60 localizes in human atheroma and regulates macrophage tumor necrosis factor-alpha and matrix metalloproteinase expression // Circulation. 1998. Vol. 98, N 4. P. 300–307.
19. Clancy R., Ren Z., Pang G. et al. Chronic Chlamydia pneumoniae infection may promote coronary artery disease in humans through enhancing secretion of interleukin-4 // Clin. Experim. Immunol. 2006. Vol. 146, N 2. P. 197–202.
20. Vainas T., Kurvers H. A., Mess W. H. et al. Chlamydia pneumoniae serology is associated with thrombosis-related but not with plaque-related microembolization during carotid endarterectomy // Stroke. 2002. Vol. 33, N 5. P. 1249–1254.
21. Tiran A., Gruber H. J., Graier W. F. et al. Aspirin inhibits Chlamydia pneumoniae-induced nuclear factor-kappa B activation, cytokine expression, and bacterial development in human endothelial cells // Arterioscler. Thromb. Vasc. Biol. 2002. Vol. 22, N 7. P. 1075–1080.
22. Espinola-Klein C., Rupprecht H. J., Blankenberg S. et al. Are morphological or functional changes in the carotid artery wall associated with Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, or herpes simplex virus infection? // Stroke. 2000. Vol. 31, N 9. P. 2127–2133.
23. Markus H. S., Sitzer M., Carrington D. et al. Chlamydia pneumoniae infection and early asymptomatic carotid atherosclerosis // Circulation. 1999. Vol. 100, N 8. P. 832–837.
24. Sander D., Winbeck K., Klingelhöfer J. et al. Enhanced progression of early carotid atherosclerosis is related to Chlamydia pneumoniae (Taiwan acute respiratory) seropositivity // Circulation. 2001. Vol. 103, N 10. P. 1390–1395.
25. Schmidt C., Hulthe J., Wikstrand J. et al. Chlamydia pneumoniae seropositivity is associated with carotid artery intima-media thickness // Stroke. 2000. Vol. 31, N 7. P. 1526–1531.
26. Cook P. J., Honeybourne D., Lip G. Y. et al. Chlamydia pneumoniae antibody titers are significantly associated with acute stroke and transient cerebral ischemia: the West Birmingham Stroke Project // Stroke. 1998. Vol. 29, N 2. P. 404–410.
27. Elkind M. S., Lin I. F., Grayston J. T., Sacco R. L. Chlamydia pneumoniae and the risk of first ischemic stroke: The Northern Manhattan Stroke Study // Stroke. 2000. Vol. 31, N 7. P. 1521–1525.
28. Strachan D. P., Carrington D., Mendall M. A. et al. Relation of Chlamydia pneumoniae serology to mortality and incidence of ischaemic heart disease over 13 years in the caerphilly prospective heart disease study // B. M. J. 1999. Vol. 318, N 7190. P. 1035–1040.
29. Alamowitch S., Labreuche J., Touboul P. J. et al. Chlamydia pneumoniae seropositivity in aetiological subtypes of brain infarction and carotid atherosclerosis: a case–control study // J. Neurol. Neurosurg. Psychiatry. 2008. Vol. 79, N 2. P. 147–151.
30. Wald N. J., Law M. R., Morris J. K. et al. Chlamydia pneumoniae infection and mortality from ischemic heart disease: large prospective study // B. M. J. 2000. Vol. 321, N 7255. P. 204–207.
31. Brykczyński M., Żych A., Gorący I. Evaluation of the level of antibodies against Chlamydophila (Chlamydia) pneumoniae in post-surgery heart ischaemia patients and their clinical conditions – a six-year study // Arch. Med. Sci. 2010. Vol. 6, N 2. P. 214–220.
32. Siscovick D. S., Schwartz S. M., Caps M. et al. Chlamydia pneumoniae and atherosclerotic risk in populations: the role of seroepidemiology // J. Infect. Dis. 2000. Vol. 181. Suppl. 3. P. s417–s420.
33. Boman J., Hammerschlag M. R. Chlamydia pneumoniae and atherosclerosis: critical assessment of diagnostic methods and relevance to treatment studies // Clin. Microbiol. Rev. 2002. Vol. 15, N 1. P. 1–20.
34. Maraha B., Berg H., Kerver M. et al. Is the perceived association between Chlamydia pneumoniae and vascular diseases biased by methodology? // J. Clin. Microbiol. 2004. Vol. 42, N 9. P. 3937–3941.
35. LaBiche R., Koziol D., Quinn T. C. et al. Presence of Chlamydia pneumoniae in human symptomatic and asymptomatic carotid atherosclerotic plaque // Stroke. 2001. Vol. 32, N 4. P. 855–860.
36. Bartels C., Maass M., Bein G. et al. Association of serology with the endovascular presence of Chlamydia pneumoniae and cytomegalovirus in coronary artery and vein graft disease // Circulation. 2000. Vol. 101, N 2. P. 137–141.
37. Prager M., Türel Z., Speidl W. S. et al. Chlamydia pneumoniae in carotid artery atherosclerosis: a comparison of its presence in atherosclerotic plaque, healthy vessels, and circulating leukocytes from the same individuals // Stroke. 2002. Vol. 33, N 12. P. 2756–2761.
38. Smieja M., Mahony J., Petrich A. et al. Association of circulating Chlamydia pneumoniae DNA with cardiovascular disease: a systematic review // BMC Infect. Dis. 2002. Vol. 2. P. 21.
39. Kuo C. C., Grayston J. T., Campbell L. A. et al. Chlamydia pneumoniae (TWAR) in coronary arteries of young adults (15–34 years old) // Proc. Natl. Acad. Sci. U.S.A. 1995. Vol. 92, N 15. P. 6911–6914.
40. Yamashita K., Ouchi K., Shirai M. et al. Distribution of Chlamydia pneumoniae infection in the athersclerotic carotid artery // Stroke. 1998. Vol. 29, N 4. P. 773–778.
41. Kaplan M., Yavuz S. S., Cinar B. et al. Detection of Chlamydia pneumoniae and Helicobacter pylori in atherosclerotic plaques of carotid artery by polymerase chain reaction // Int. J. Infect. Dis. 2006. Vol. 10, N 2. P. 116–123.
42. Virok D., Kis Z., Karai L. et al. Chlamydia pneumoniae in atherosclerotic middle cerebral artery // Stroke. 2001. Vol. 32, N 9. P. 1973–1976.
43. Jackson L. A., Campbell L. A., Kuo C. C. et al. Isolation of Chlamydia pneumoniae from a carotid endarterectomy specimen // J. Infect. Dis. 1997. Vol. 176, N 1. P. 292–295.
44. Valassina M., Migliorini L., Sansoni A. et al. Search for Chlamydia pneumoniae genes and their expression in atherosclerotic plaques of carotid arteries // J. Med. Microbiol. 2001. Vol. 50, N 3. P. 228–232.
45. Farsak B., Yildirir A., Akyön Y. et al. Detection of Chlamydia pneumoniae and Helicobacter pylori DNA in human atherosclerotic plaques by PCR // J. Clin. Microbiol. 2000. Vol. 38, N 12. P. 4408–4411.
46. Meijer A., J. van Der Vliet A., Roholl P. J. et al. Chlamydia pneumoniae in abdominal aortic aneurysms: abundance of membrane components in the absence of heat shock protein 60 and DNA // Arterioscler. Thromb. Vasc. Biol. 1999. Vol. 19, N 11. P. 2680–2686.
47. Fong I. W., Chiu B., Viira E. et al. De Novo induction of atherosclerosis by Chlamydia pneumoniae in a rabbit model // Infect. Immun. 1999. Vol. 67, N 11. P. 6048–6055.
48. Fong I. W., Chiu B., Viira E. et al. Influence of clarithromycin on early atherosclerotic lesions after Chlamydia pneumoniae infection in a rabbit model // Antimicrob. Agents Chemother. 2002. Vol. 46, N 8. P. 2321–2326.
49. Muhlestein J. B., Anderson J. L., Hammond E. H. et al. Infection with Chlamydia pneumoniae accelerates the development of atherosclerosis and treatment with azithromycin prevents it in a rabbit model // Circulation. 1998. Vol. 97, N 7. P. 633–636.
50. Jespersen C. M., Als-Nielsen B., Damgaard M. et al. Randomised placebocontrolled multicentre trial to assess shortterm clarithromycin for patients with stable coronary heart disease: CLARICOR trial // BMJ. 2006. Vol. 332, N 7532. P. 22–27.
51. Anderson J. L., Muhlestein J. B., Carlquist J. et al. Randomized secondary prevention trial of azithromycin in patients with coronary artery disease and serological evidence for Chlamydia pneumoniae infection: The Azithromycin in Coronary Artery Disease: Elimination of Myocardial Infection with Chlamydia (ACADEMIC) study // Circulation. 1999. Vol. 99, N 12. P. 1540–1547.
52. Sander D., Winbeck K., Klingelhöfer J. et al. Progression of early carotid atherosclerosis is only temporarily reduced after antibiotic treatment of Chlamydia pneumoniae seropositivity // Circulation. 2004. Vol. 109, N 8. P. 1010–1015.
53. Fabricant C. G., Fabricant J., Litrenta M. M., Minick C. R. Virus-induced atherosclerosis // J. Exp. Med. 1978. Vol. 148, N 1. P. 335–340.
54. Lucas A., Dai E., Liu L. Y., Nation P. N. et al. Atherosclerosis in Marek’s disease virus infected hypercholesterolemic roosters is reduced by HMGCoA reductase and ACE inhibitor therapy // Cardiovasc. Res. 1998. Vol. 38, N 1. P. 237–246.
55. Njenga M. K., Dangler C. A. Intimal lipid accretion and elevated serum cholesterol in Marek’s disease virus-inoculated chickens // Vet. Pathol. 1996. Vol. 33, N 6. P. 704–708.
56. Benditt E. P., Barrett T., McDougall J. K. Viruses in the etiology of atherosclerosis // Proc. Natl. Acad. Sci. U. S. A. 1983. Vol. 80, N 20. P. 6386–6389.
57. Kotronias D., Kapranos N. Herpes simplex virus as a determinant risk factor for coronary artery atherosclerosis and myocardial infarction // In Vivo. 2005. Vol. 19, N 2. P. 351–358.
58. Binkley P. F., Cooke G. E., Lesinski A. et al. Evidence for the role of Epstein Barr Virus infections in the pathogenesis of acute coronary events // PloS One. 2013. Vol. 8, N 1. P. e54008.
59. Hirabayashi Y., Ishii T., Kodera T. et al. Acute cytomegalovirus infection and transient carotid intimal-medial thickening in a young, otherwise healthy woman // J. Clin. Microbiol. 2003. Vol. 41, N 8. P. 3978–3980.
60. Izadi M., Fazel M., Saadat S. H. et al. Cytomegalovirus localization in atherosclerotic plaques is associated with acute coronary syndromes: report of 105 patients // Methodist Debakey Cardiovasc. J. 2012. Vol. 8, N 2. P. 42–46.
61. Gulizia J. M., Kandolf R., Kendall T. J. et al. Infrequency of cytomegalovirus genome in coronary arteriopathy of human heart allografts // Am. J. Pathol. 1995. Vol. 147, N. 2. P. 461–475.
62. Siscovick D. S., Schwartz S. M., Corey L. et al. Chlamydia pneumoniae, herpes simplex virus type 1, and cytomegalovirus and incident myocardial infarction and coronary heart disease death in older adults : the Cardiovascular Health Study // Circulation. 2000. Vol. 102, N 19. P. 2335–2340.
63. Grahame-Clarke C., Chan N. N., Andrew D. et al. Human cytomegalovirus seropositivity is associated with impaired vascular function // Circulation. 2003. Vol. 108, N 6. P. 678–683.
64. Ridker P. M., Hennekens C. H., Stampfer M. J., Wang F. Prospective study of herpes simplex virus, cyto megalovirus, and the risk of future myocardial infarction and stroke // Circulation. 1998. Vol. 98, N 25. P. 2796–2799.
65. Al-Ghamdi A. Role of herpes simplex virus-1, cytomegalovirus and Epstein-Barr virus in atherosclerosis // Pak. J. Pharm. Sci. 2012. Vol. 25, N 1. P. 89–97.
66. Hsu H. Y., Nicholson A. C., Pomerantz K. B. et al. Altered cholesterol trafficking in herpesvirus-infected arterial cells. Evidence for viral protein kinase-mediated cholesterol accumulation // J. Biol. Chem. 1995. Vol. 270, N 33. P. 19630–19637.
67. Weis M., Kledal T. N., Lin K. Y. et al. Cytomegalovirus infection impairs the nitric oxide synthase pathway: role of asymmetric dimethylarginine in transplant arteriosclerosis // Circulation. 2004. Vol. 109, N 4. P. 500–505.
68. Cayatte A. J., Palacino J. J., Horten K., Cohen R. A. Chronic inhibition of nitric oxide production accelerates neointima formation and impairs endothelial function in hypercholesterolemic rabbits // Arterioscler. Thromb. 1994. Vol. 14, N 5. P. 753–759.
69. Bolovan-Fritts C. A., Trout R. N., Spector S. A. Human cytomegalovirus-specific CD4+-T-cell cytokine response induces fractalkine in endothelial cells // J. Virol. 2004. Vol. 78, N 23. P. 13173–13181.
70. Bolovan-Fritts C. A., Trout R. N., Spector S. A. High T-cell response to human cytomegalovirus induces chemokine-mediated endothelial cell damage // Blood. 2007. Vol. 110, N 6. P. 1857–1863.
71. Bolovan-Fritts C. A., Spector S. A. Endothelial damage from cytomegalovirus-specific host immune response can be prevented by targeted disruption of fractalkine-CX3CR1 interaction // Blood. 2008. Vol. 111, N 1. P. 175–182.
72. Van de Berg P. J., Yong S. L., Remmerswaal E. B. et al. Cytomegalovirus-induced effector T cells cause endothelial cell damage // Clin. Vaccine Immunol. 2012. Vol. 19, N 5. P. 772–779.
73. Botto S., Streblow D. N., DeFilippis V. et al. IL-6 in human cytomegalovirus secretome promotes angiogenesis and survival of endothelial cells through the stimulation of survivin // Blood. 2011. Vol. 117, N 1. P. 352–361.
74. Visser M. R., Tracy P. B., Vercellotti G. M. et al. Enhanced thrombin generation and platelet binding on herpes simplex virus-infected endothelium // Proc. Natl. Acad. Sci. U. S. A. 1988. Vol. 85, N 21. P. 8227–8230.
75. Pryzdial E. L., Wright J. F. Prothrombinase assembly on an enveloped virus: evidence that the cytomegalovirus surface contains procoagulant phospholipid // Blood. 1994. Vol. 84, N 11. P. 3749–3757.
76. Sutherland M. R., Raynor C. M., Leenknegt H. et al. Coagulation initiated on herpesviruses // Proc. Natl. Acad. Sci. U.S.A. 1997. Vol. 94, N 25. P. 13510–13514.
77. Livingston J. R., Sutherland M. R., Friedman H. M., Pryzdial E. L. Herpes simplex virus type 1-encoded glycoprotein C contributes to direct coagulation Factor X–virus binding // Biochem. J. 2006. Vol. 393, pt. 2. P. 529–535.
78. Alber D. G., Powel K. L., Goodwin D. A. et al. Herpesvirus infection accelerates atherosclerosis in the apolipoprotein E-deficient mouse // Circulation. 2000. Vol. 102, N 7. P. 779–785.
79. Alber D. G., Vallance P., Powell K. L. Enhanced atherogenesis is not an obligatory response to systemic herpesvirus infection in the apoE-deficient mouse: comparison of murine gamma-herpesvirus-68 and herpes simplex virus-1 // Arterioscler. Thromb. Vasc. Biol. 2002. Vol. 22, N 5. P. 793–798.
80. Madjid M., Aboshady I., Awan I. et al. Influenza and cardiovascular disease: is there a causal relationship? // Tex. Heart Inst. J. 2004. Vol. 31, N 1. P. 4–13.
81. Phrommintikul A., Kuanprasert S., Wongcharoen W. et al. Influenza vaccination reduces cardiovascular events in patients with acute coronary syndrome // Eur. Heart J. 2011. Vol. 32, N 14. P. 1730–1757.
82. Naghavi M., Wyde P., Litovsky S. et al. Influenza infection exerts prominent inflammatory and thrombotic effects on the atherosclerotic plaques of apolipoprotein E-deficient mice // Circulation. 2003. Vol. 107, N 5. P. 762–768.
83. Keller T. T., van der Meer J. J., Teeling P. et al. Selective expansion of influenza A virus-specific T cells in symptomatic human carotid artery atherosclerotic plaques // Stroke. 2008. Vol. 39, N 1. P. 174–179.
84. Lee M. H., Yang H. I., Wang C. H. et al. Hepatitis C virus infection and increased risk of cerebrovascular disease // Stroke. 2010. Vol. 41, N 12. P. 2894–2900.
85. Arcari C. M., Nelson K. E., Netski D. M. et al. No association between hepatitis C virus seropositivity and acute myocardial infarction // Clin. Infect. Dis. 2006. Vol. 43, N 6. P. 53–56.
86. Boddi M., Abbate R., Chellini B. et al. Hepatitis C virus RNA localization in human carotid plaques // J. Clin. Virol. 2010. Vol. 47, N 1. P. 72–75.
87. Ishizaka Y., Ishizaka N., Takahashi E. et al. Association between hepatitis C virus core protein and carotid atherosclerosis // Circ. J. 2003. Vol. 67, N 1. P. 26–30.
88. Markus H. S., Mendall M. A. Helicobacter pylori infection: a risk factor for ischaemic cerebrovascular disease and carotid atheroma // J. Neurol. Neurosurg. Psychiatry. 1998. Vol. 64, N 1. P. 104–107.
89. Ameriso S. F., Fridman E. A., Leiguarda R. C., Sevlever G. E. Detection of Helicobacter pylori in human carotid atherosclerotic plaques // Stroke. 2001. Vol. 32, N 2. P. 385–391.
90. Weiss T. W., Kvakan H., Kaun C. et al. No evidence for a direct role of Helicobacter pylori and Mycoplasma pneumoniae in carotid artery atherosclerosis // J. Clin. Pathol. 2006. Vol. 59, N 11. P. 1186–1190.
91. Whincup P. H., Mendall M. A., Perry I. J. et al. Prospective relations between Helicobacter pylori infection, coronary heart disease, and stroke in middle aged men // Heart. 1996. Vol. 75, N 6. P. 568–572.
92. Blasi F., Denti F., Erba M. et al. Detection of Chlamydia pneumoniae but not Helicobacter pylori in atherosclerotic plaques of aortic aneurysms // J. Clin. Microbiol. 1996. Vol. 34, N 11. P. 2766–2769.
93. Espinola-Klein C., Rupprecht H. J., Blankenberg S. et al. Impact of infectious burden on progression of carotid atherosclerosis // Stroke. 2002. Vol. 33, N 11. P. 2581–2586.
94. Khairy P., Rinfret S., Tardif J. C. et al. Absence of association between infectious agents and endothelial function in healthy young men // Circulation. 2003. Vol. 107, N 15. P. 1966–1971.