Теоретические основы создания вакцины для лечения атеросклероза
- Авторы: Нагорнев В.А.1
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Учреждения:
- ГУ «Научно-исследовательский институт экспериментальной медицины РАМН»
- Выпуск: Том 7, № 2 (2007)
- Страницы: 78-94
- Раздел: Лекция
- Статья опубликована: 15.05.2007
- URL: https://journals.eco-vector.com/MAJ/article/view/693231
- ID: 693231
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Аннотация
Автор, на основании своего опыта работы в области изучения морфо- и патогенеза атеросклероза, с учетом анализа литературы, представил свое видение проблемы профилактики и лечения атеросклероза. В настоящее время нельзя отрицать того, что без учета тех глубоких сдвигов в иммунной системе, которые происходят в процессе болезни, невозможно разрабатывать стратегию лечения атеросклероза. Основываться только на показателях уровня липидов в крови, назначая терапию пациенту, это значит вернуться в XX век. Но, с другой стороны, разработка современных патогенетически обоснованных методов лечения атеросклероза требует создания новой методологии, на основе которой возможна разработка вакцины против атеросклероза.
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Об авторах
В. А. Нагорнев
ГУ «Научно-исследовательский институт экспериментальной медицины РАМН»
Автор, ответственный за переписку.
Email: medaj@eco-vector.com
Академик РАМН
Россия, Санкт-ПетербургСписок литературы
- Нагорнев В. А. Патогенез атеросклероза. СПб.: Хромикс, 2006.
- Afek A., Harats D., Roth A. et al. Evidence for the involvement of T cell costimulation through the B-7/CD28 pathway in atherosclerotic plaques from apolipoprotein E knockout mice // Exp. Mol. Pathol. 2004. Vol. 76. P. 219-223.
- Aikawa M. et al. An HMG-CoA reductase inhibitor, cerivastatin, suppresses growth of macrophages expressing matrix metalloproteinases and tissue factor in vivo and in vitro // Circulation. 2001. Vol. 103. P. 276-283.
- Ameli S., Hultgardh-Nilsson S., Regnstrom J, et al. Effect of immunization with homologous LDL and oxidized LDL on early atherosclerosis in hypercholesterolemic rabbits // Arterioscler. Thromb. Vase. Biol. 1996. Vol. 16. P. 1074-1079.
- Arkin M. R., and Wells J. A. Small-molecule inhibitors of protein interaction: progressing towards the dream // Nat. Rev. Drug. Discov. 2004. Vol. 3.P. 301-317.
- Asadullah K., Sterry W. and Volk H. D. Interleukin-10 therapy-review of a now approach // Pharmacol. Rev. 2003. Vol. 5 5. P. 241-269.
- Baetz A., Frey M., Heeg K., and Dalpke A. H. Supressor of cytokine signaling (SOCS) proteins indirectly regulate toll-like receptor signaling in innate immune cells // J. Biol. Chem. 2004. Vol. 279. P. 54708-54715.
- Barter P, Rye К A. Cholesterol ester transfer protein: its role in plasma lipid transport // Clin. Exp. Pharmacol. Physiol. 1994. Vol. 21. P. 663-672.
- Beutler B., Hoebe K., Georgel P. et al. Genetic analysis in innate immunity: identification and function of the TIR adapter proteins // Adv. Exp. Med. Biol. 2005. Vol. 560. R 29-39.
- Binder C. J., Horkko S., Dewan A. et al. Pneumococcal vaccination decreases atherosclerotic lesion formation: molecular mimicry between Streptococcus pneumoniae and oxidized LDL // Nat. Med. 2003. Vol. 9. R 736-743.
- Binder С. J. et al. The role of netural antibodies in atherogenesis // J. Lipid. Res. 2005. Vol. 46. P. 1353-1363.
- Bjorkbacka H., K unjathoo V. K, Moore K. J. et al. Reduction atherosclerosis in MyD88-null mice links elevated serum cholesterol levels to activation of innate immunity signaling pathways // Nat. Med. 2004. Vol. 10. P. 416-421.
- Bogdan C., and Nathan C. Modulation of macrophage function by transforming growth factor beta, interleukin-4, and interleukin-10 // Ann. NY Acad. Sci. USA. 1993. Vol. 685. P. 713-739.
- Bourcier T., Sukhova G., and Libby P. The nuclear factor kappa-B signaling pathway participates in dysregulation of vascular smooth muscle cells in vitro and in hum an atherosclerosis // J. Biol. Chern. 1997. Vol. 272. P. 15817-15824.
- Brand K., Page S., Rogier G. et al. Activated transcription factor nuclear factor-kappa В is present in the atherosclerotic lesion // J. Clin. Invest. 1996. Vol. 97. P. 1715-1722.
- Brown M. L., Inazu A., H ester С. B. et al. Molecular basis of lipid transfer protein deficiency in a family with increased high-density lipoproteins //Nature. 1989. Vol. 342. P. 448-451.
- Burns K. et al. Inhibition of interleukin 1 receptor/Toll-like receptor signaling through the alternatively spliced, short form of MyD88 is due to its failutr to recruit IRA K -4 // J. Exp. Med. 2003. Vol. 197. P 263-268.
- Caligiuri G., Rudling M., Ollivier V, et al. Interleukin-10 deficiency increases atherosclerosis, thrombosis, and low -density lipoproteins in apolipoprotein E knockout mice // Mol. Med. 2003. Vol. 9. P. 10-17.
- Chen Y. et al. Peripheral deletion of antigen-reactive T cells in oral tolerance // Nature. 1995. Vol. 376. P. 177-180.
- Chuang T. H., and Ulevitch R. J. Triad3A, an E3 ubiquitin-protein ligase regulating Toll-like receptors // N at. Immunol. 2004. Vol. 5. P. 495-502.
- Chyu K. Y. et al. Timing affacts the efficacy of LDL immunization on atherosclerotic lesions in apo Е(~Л) m ice // Atherosclerosis. 2004. Vol. 176. P. 27-35.
- Constant S. L., and Bottomly K. Induction of Th1 and Th2 CD4+ T cell responses: the aiternative approaches // Ann. Rev. Immunol. 1997. Vol. 15. P. 297-322.
- Cunha E Q., Moncada S., Liew E Y Interleukin-10 (IL -10) inhibits the induction of nitric oxide synthase by interferon-y in murine macrophages // Biochem. Biophys. Res. Commun. 1992. Vol. 182. P 1155-1159.
- Daugherty A., Rateri D. T lymphocytes in atherosclerosis. The Yin-Yang of Th1 and Th2 influence on lesion formation // Circ. Res. 2002. Vol. 90. P 1039-1040.
- DiChiara M. R., Kiely J, M., Gimbrone M. A. et al. Inhibition of E-selectin gene espression by transforming growth factor beta in endothelial cells involves coactivator integration of smad and nuclear factor kappaB-mediated signals // J. Exp. Med. 2000. Vol. 192. P 695-704.
- Divanovic S. et al. Negative regulation of Toll-like receptor 4 signaling by the Toll-like receptor homolog RP105 // Nat. Immunol. 2005. Vol. 6. P 571-578.
- Edfeldt K., Swedenborg J., Hansson G. К et al. Expression of toll-like receptors in human atherosclerotic lesions: a possible pathway for plaque activation // Circulation. 2002. Vol. 105. P. 1158-1161.
- Fong L. G., Parthasaraty S., Witztum J.L., Ste inberg D. Non enzymatic oxidative cleavage of peptide bonds in apoprotein B-100 // J. Lipid. Res. 1987. Vol. 12. P. 1466-1477.
- Fredrikson G. N., Soderberg L, Lindholm M. et al. Inhibition of atherosclerosis in ApoE-null mice by immunization with ApoB-100 peptide sequences // Arterioscler. Thromb. Vase. Biol. 2003. Vol. 23. P. 879-884.
- Freigang S., Horkko S., Miller E. et al. Immunization of LDL receptor-deficient mice with homologous malandialdehyde-modified and native LDL reduces progression of atherosclerosis by mechanisms other than induction of high titers of antibodies to oxidative neoepitopes // Arterioscler. Thromb. Vase. Biol. 1998. Vol. 18. P 1972-1982.
- Frostegard J. Autoimmunity, oxidized LDL and cardiovascular disease/ / Autoimmun. Rev. 2002. Vol. 1. P. 233-237.
- Frostegard J., Ulfgren A. K., Nyberg P et al. Cytokine expression in advanced human atherosclerotic plaques: dominance of pro-inflammatory (T hl) and macrophage-stimulating cytokines // Atherosclerosis. 1999. Vol. 145. P. 33-43.
- Fucao T. and Koyasu S. PI3K and negative regulation of TLR signaling // Trends. Immunol. 2003. Vol. 24. P. 358-363.
- Fucumoto M., Shoji T, Emoto M. et al. Antibodies against oxidized LDL and carotid artery intima-media thickens in a heaithy population It Arterioscler. Thromb. Vase. Biol. 2000. Vol. 20. P 703-707.
- George J., Afek A., Gilurd B. et al. Induction of early atherosclerosis in LDL-receptor deficient mice immunized with P2-glycoprotein 1 // 1998. Vol. 11. P 1108-1115.
- George J. et al. Supression of early atherosclerosis in LDL-receptor deficient mice by oral tolerance with P2-glycoprotein 1 // Cardiovasc. Res. 2004. Vol. 62. P. 603-609.
- Genolet R., Wahli W, and Michalik L. PPARs as drug targets to modulate inflammatory responses? // Curr. Drug. Targets Inflamm. Allergy. 2004. Vol. 3. P. 361-375.
- Grooth G. J., Klerkx A. H., Stroes E. S. et al. A review of CETP and its relation to atherosclerosis // J. Lipid. Res. 2004. Vol. 45. P. 1967-1974.
- Han J., and Ulevitch R. Limiting inflammatory responses during activation of innate immunity // Nat. Immunol. 2005. Vol. 6. P. 1198-1205.
- Hansen P. R., Chew M., Zhou J. et al. Freunds adjuvant alone is antiatherogenic in apoE-deficient mice and specific immunization against TNF-a confers no additional benefit // Atherosclerosis. 2001. Vol. 15 8. P. 87-94.
- Hansson G. K. Vaccination against atherosclerosis. Science of fiction? // Circulation. 2002. Vol. 106. P. 337-356.
- Hansson G. K. Inflammation, atherosclerosis, and coronary disease // N. Engl. J. Med. 2005. Vol. 352. P. 1685-1695.
- Hansson G. K., and Libby P. The immune response in atherosclerosis: a double-edged sword // Nat. Rev. Immunol. 2006. Vol. 6. P. 508-519.
- Hansson G. K., Libby P, Shonbeck U., Yan Z. Q. Innate and adaptive immunity in the pathogenesis of atherosclerosis // 2002. Vol. 91. P. 1281-1291.
- Harais D., Yacov N., Gilburn B. Oral tolerance with heat shock protein-65 attenuates Mycobacterium tuberculosis-induced and high-fat-diet- driven atherosclerotic lesions // J. Am. Coll. Cardiol. 2002. Vol. 40. P. 1333-13 38.
- Hauer A. D., Uyttenhove C., de Vos P et al. Blocade of interleukin-12 function by protein vaccination attenuates atherosclerosis // Circulation. 2005. Vol. 112. P. 1054-1062.
- Heeschen C., Dimmeler S., Hamm C. W. The CAPTURE Study Investigators: Serum level of the anti-inflammatory cytokine interleukin-10 is an important prognostic determinant in patients with acute coronary syndromes // Circulation. 2003. Vol. 107. P. 2109-2114.
- Honda H. M., Leitinger N., Frankel M. et al. Induction of monocyte binding to endothelial cells by MM-LDL: role of lipoxygenase metabolites // Arterioscler. Thromb. Vase. Biol. 1999. Vol. 19. P. 680-686.
- Hulthe J., Wilkund O., Hurt-Camejo E., Bondjers G. Antibodies to oxidized LDL in relation to carotid atherosclerosis, cell adhesion molecules, and phospholipase A2 // Arterioscler. Thromb. Vase. Biol. 2001. Vol. 21. P. 269-274.
- Iwami К. I. et al. Cutting edge: naturally occurring soluble form of mouse Toll-like receptor 4 inhibits lipopolysaccaride signaling // J. Immunol. 2000. Vol. 165. P. 6682-6686.
- Janssens S., Burns K., Vercammen E. et al. MyD88S, a splice variant of MyD88, differentially modulates NF-кВ and AP-1 dependent gene expression // FEBSb Lett. 2003. Vol. 548. P. 103-107.
- Kotlyarov A., Neininger A., Schubert C., and Gaestel M. MAPKAP kinase 2 is essential for LPS-induced TNF-a biosynthesis // Nat. Cell. Biol. 1999. Vol. 1. P. 94-97.
- Latchman D. S. Transcription factors as potential targets for therapeutic drugs // Curr. Pharm. Biotechnol. 2000. Vol. 1. P. 57-61.
- Li Q., and Verma I. M. NF-кВ regulation in the immune system // Nat. Rev. Immunol. 2002. Vol. 2. P. 725-734.
- Liew E Y., Xu D., Brint E. K., and O ’Neill L. A. Negative regulation of toll-like receptor-mediated immune responses // Nat. Rev. Immunol. 2005. Vol. 5. P. 446-458.
- Loiarro M. et al. Peptide-mediated interference of TIR domain dimerization in MyD88 inhibits interleukin-1 dependent activation of NF-кВ // J. Biol. Chern. 2005. Vol. 280. P. 15809-15814.
- Mach E Statins as immunomodulatory agents // Circulation. 2004. Vol. 109. Suppl. //. P. 1115-1117.
- Mach E, Schonbeck U., Sukhova G. К et al. Reduction of atherosclerosis in mice by inhibition of CD40 signaling // Nature. 1998. Vol. 394. P. 200-203.
- Mallat Z., Besnard S., Duriez M. et al. Protective role of interleukin-10 in atherosclerosis // Circ. Res. 1999. Vol. 85. P. el7-e24.
- Maron R., Sukhova G., Faria A. et al. Mucosal administration of heat shock protein-65 decreases atherosclerosis and inflammation in aorta arch of lowOdensity lipoprotein receptor-deficient mice //Circulation. 2002. Vol. 106. P. 1708-1715.
- Metz P M., DeWitt D. L., Stetler-Stevenson W G. et al. Interleukin-10 supression of monocyte prostaglandin-dependent matrix metalloproteinase production // Science. 1994. Vol. 269. P. 21322-21329.
- Michelsen K. S., Wong M. H., Shah P К et al. Lack of Toll-like receptor 4 or myeloid differentiation factor 88 reduces atherosclerosis and alters plaque phenotype in mice deficient in apolipoprotein E // Proc. Natl. Acad. Sci. USA. 2004. Vol. 101. P. 10679-10684.
- Miller D. L., Yaron R., Yellin M. J. CD40L-CD40 interactions regulate endothelial cell surface tissue factor and thrombomodulin expression // J. Leukoc. Biol. 1998. Vol. 63. P. 373-379.
- Monaco C., Andreakos E., Kiriakidis S. et al. Canonical pathway of nuclear factor kappa В activation selectively regulates ptoinflammatory and prothrombotic responses in human atherosclerosis // Proc. Natl. Acad. Sci. USA. 2004. Vol. 101. P. 5634-5639.
- Neto J. R. F. et al. Passive immunization with monoclonal (IgM) antibody accelerated atherosclerosis in vein-graft model in apo E null mice // Circulation. 2004. Vol. 110. R Ш - 52.
- Nilsson J., Hansson J. K., Shah P K. Immunomodulation of atherosclerosis. Implications for vaccine developm ent // Arterioscler. Thromb. Vase. Biol. 2005. Vol. 25. P. 18-28.
- Nilsson J., Calara F., Regnstrom J. et al. Immunization with homologous oxidized low density lipoprotein reduces neointimal formation after ballon in hypercholesterolemic rabbits // J. Am. Coll. Cardiol. 1997. Vol. 30. R 1886-1891.
- Okabe T., Kishimoto C., Shimada K. et al. Effects of late administration of immunoglobulin on experimental atherosclerosis in apolipoprotein E-deficient mice // Exp. Invest. 2005. Vol. 69. R 1543-1546.
- Palinski W., Witztum J. L. Immune responses to oxidative neoepitopes on LDL and phospholipids modulate the developm ent of atherosclerosis // J. Intern. Med. 2000. Vol. 247. R 371-380.
- Palinski Ж, Miller E., Witztum J, L. Immunization of low density lipoprotein (LDL) receptordeficient rabbits with homolohous malondialde-hyde-modified LDL and oxidized LDL on early atherosclerosis in hypercholesterolemic rabbits // Proc. Natl. Acad. Sci. USA. 1995. Vol. 92. P. 821-825.
- Pinderski-Oslund L. J., Hendrick С. C., Olvera T et al. Interleukin-10 blocks atherosclerotic events in vitro and in vivo // Arterioscler. Thromb. Vase. Biol. 1999. Vol. 19. R 2847-2853.
- Pinderski L, J., Fischbein M, P, Subbanagounder G. et al. Overexpression of interleukin-10 by activated T lym phocytes inhibits atherosclerosis in LDL receptor-deficient mice by altering lymphocyte and macrophage phenotypes // Circ. Res. 2002. Vol. 90. R 1064-1071.
- Pradier O., Gerard C., Delvaux A. et al. Interleukin-10 inhibits the induction of monocyte procoagulant activity by bacterial lipopolysaccharide // Eur. J. Immunol. 1993. Vol. 23. R 2700—2703.
- Reyes O. S., Chyu К Y., Yano J. et al. Immunization with a novel hum an A po В 100 related peptide reduces atherosclerosis and inflammation in apo E null mice // 2002. Vol. 39 (Suppl. A). S. 240A.
- Rittershaus C., Miller D. P, Thomas L. J. et al. Vaccine-induced antibodies inhibit CETP activity in vivo and reduce aortic lesions in a rabbit model of atherosclerosis // Atheroscler. Thromb. Vase. Biol. 2000. Vol. 20. R 2106-2112.
- Sattar N., McCarey D. W, Capell H., and McLnnes I. B. Explaining how «high-grade» systemic inflammation accelerates vascular risk in rheumatoid arthritis // Circulation. 2003. Vol. 108. R 2957-2963.
- Schipou A. et al. Recombinant human antibodies against aldegyde-modified apolipoprotein B-100 peptide sequences inhibit atherosclerosis // Circulation. 2004. Vol. 110. R 2047-2052.
- Shah R K., Chyu K-Y., Fredrikson G. IL, and Nilsson J. Immunomodulation of atherosclerosis with a vaccine // 2005. Vol. 2. R 639-646.
- Shaw P. X., Horkko S., Chang M. K. et al. Natural antibodies with the T15 idiotype may act in atherosclerosis, apoptotic clearance, and protective immunity // J. Clin. Invest. 2000. Vol. 105. R 1731-1740.
- Schmidt-Weber С. B. and Blaser K. Regulation and role of transforming growth factor-p in immune tolerance induction and inflammation // Curr. Opin. Immunol. 2004. Vol. 16. R 709-716.
- Silvestre J. S., Mallat Z., Tamarat R. et al. Regulation of matrix metalloproteinase activity in ischemic tissue by interleukin-10: role in ischemia-induced angiogenesis // Circ. Res. 2001. Vol. 89. R 259-264.
- Stemme S., Faber B., Holm J. et al. T lymphocytes from human atherosclerotic plaques recognize oxidized low density lipoprotein // Proc. Natl. Acad. Sci. USA. 1995. Vol. 92. R 3893-3897.
- Suzuki N., Suzuki S., and Yeh W. C IRAK-4 as the central TIR signaling mediator in innate immunity // Trends Immunol. 2002. Vol. 23. P. 503-506.
- Tall A. R. Plasma Cholesteryl ester transfer protein and high-density lipoproteins: new insights from molecular genetic studies // J. Intern. Med. 1995. Vol. 237. R 5-12.
- Tomvall P, Waeg G., Nilsson J. et al. Auto-antibodies against modified low-density lipoproteins in coronary artery disease // Atherosclerosis. 2003. Vol. 167. R 347-353.
- Tupin E., Nicoletti A., Eihage R. et al. CD1- dependent activation of NKT cell aggravates atherosclerosis // J. Exp. Med. 2004. Vol. 199. R 417-422.
- Wesche H et al. IRAK-M is a novel member of the Pelle/interleukin-1 receptor-associated kinase (IRAK) family // J. Biol. Chern. 1999. Vol. 274. R 19403-19410.
- Хи G., Dietrich Н., Steiner Н. J. et al. Induction of atherosclerosis in normocholesterolemic rabbits by immunization with heat shock protein 65 // Arterioscler. Thromb. 1992. Vol. 12. P. 789-799.
- Xu Q., WilleitJ, Marosi M. et al. Association of serum antibodies to heat-shock protein 65 with carotid atherosclerosis // Lancet. 1993. Vol. 341. P. 255-259.
- Xu X. H., Shah R X., Faure E. et al. Toll-like receptor-4 is expressed by macrophages in murine and human lipid-rich atherosclerotic plaques and upregulated by oxidized LDL // Circulation. 2001. Vol. 104. P. 3103-3108.
- Yoshida M. Potential role of statines in inflammation and atherosclerosis // J. Atheroscler. Thromb. 2003. Vol. 10. P. 140-144.
- Youssef E, Stuve O., Patarroyo J. C. et al. The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease // Nature. 2002. Vol. 420. P. 78-84.
- Zhou X. H., Paulsson G., Stemme S., Hansson G. K. Hypercholesterolem ia is associated with a T helper (Th)l/Th2 swich of the autoimmune response in atherosclerotic apo E-knockout mice // J. Clin. Invest. 1998. Vol. 101. P. 1717-1725.
- Zhou X., Caligiuri G., Hamsten A. et al. LDL immunization induces T-cell-dependentantibody formation and protection against atherosclerosis // Arterioscler. Thromb. Vase. Biol. 2001. Vol. 21. P. 108-114.
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