Иммуногенные липидные маркеры атеросклероза у больных сахарным диабетом 2-го типа при программном гемодиализе
Иммуногенные липидные маркеры атеросклероза у больных сахарным диабетом 2-го типа при программном гемодиализе
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Аннотация
Цель исследования. Определение десиалированного аполипопротеина В-100 (апоВ-100) и липопротеидсодержащих циркулирующих иммунных комплексов (ЦИК-ЛПНП) у пациентов с хронической болезнью почек (ХБП) на программном гемодиализе (ПГ) с сахарным диабетом (СД) 2-го типа и без него.
Материалы и методы. Обследован 81 пациент с ХБП (50 мужчин / 31 женщина), получавших лечение ПГ, из них 36 (17/19) – с СД 2-го типа, 45 (33/12) – без СД 2-го типа. Определяли уровни общего холестерина (ОХС), триглицеридов (ТГ) и десиалированного апоВ-100 в плазме крови и ЦИК-ЛПНП. Для оценки степени развития атеросклероза использовали цветное дуплексное сканирование брахиоцефальных артерий (ЦДС БЦА) с определением толщины интимо-медиального комплекса (ИМК).
Результаты и обсуждение. Пациенты с СД 2-го типа имели высокие значения ОХС, ТГ (p<0,05). ЦДС БЦА показал увеличение толщины ИМК у всех пациентов, леченных ПГ, однако у больных СД толщина оказалась больше на 13% (p<0,05). У больных СД 2-го типа превалируют бляшки со стенозом до 50%, по сравнению с пациентами без СД (p<0,05). У пациентов с СД 2-го типа выявлен повышенный уровень цмЛПНП и ЦИК-ЛПНП в сравнении с пациентами без СД, получающими ПГ. Частота встречаемости достоверно выше для десиалированного апоВ-100 на 46% у больных с СД на гемодиализе по сравнению без СД (p<0,05). Отмечено повышение уровня ЦИК-ЛПНП на 39% (p<0,05) у пациентов с СД 2-го типа, по сравнению с больными без СД на фоне ПГ. Установлена средней силы корреляционная связь между десиалированным апоВ-100 и параметрами ЦДС БЦА (r=0,325), а также между уровнем ХС и наличием стенозов до 50% (r=0,465) у больных СД 2-го типа. Выявлено, что у пациентов с СД, получающих ПГ, острый инфаркт миокарда развивался на 79% чаще, чем у пациентов без СД (p<0,05).
Заключение. Ускоренное развитие атеросклероза при СД 2-го типа и ХБП, подтвержденное при помощи ЦДС БЦА, может быть связано с повышением уровня атерогенных цмЛПНП.
Ключевые слова: сахарный диабет 2-го типа, программный гемодиализ, атеросклероз, модифицированные липопротеиды низкой плотности, липопротеидсодержащие циркулирующие иммунные комплексы.
Materials and methods. We examined 81 patients with CKD (50 men / 31 women) treated with program hemodialysis, of which 36 (17/19) with type 2 diabetes mellitus, 45 (33/12) non-diabetic patients. The levels of total cholesterol, triglycerides and desialylated apoB-100 in blood plasma and lipoprotein-containing circulating immune complexes. A color duplex scan of brachiocephalic arteries was used to assess the extent of development of atherosclerosis with the determination of the thickness of the intima–medial complex.
Results and discussion. Patients with diabetes had high values of total cholesterol, triglycerides (p<0.05). Duplex scan of brachiocephalic arteries showed an increase in the thickness of intima-medial complex in all patients for program hemodialysis, however, in patients with diabetes, the thickness was 13% higher (p<0.05). In patients with diabetes, plaques with stenosis up to 50% prevail, compared with non-diabetic patients, p<0.05. The incidence was significantly higher for desialized apoB-100 by 46% in patients with diabetes on hemodialysis compared non-diabetic patients (p<0.05). An increase in the level of lipoprotein-containing circulating immune complexes by 39%, (p<0.05) in patients with diabetes mellitus was observed, compared with patients non-diabetic patients. The correlation between desialized apoB-100 and duplex scan of brachiocephalic arteries parameters (r=0.325), as well as between the cholesterol level and stenosis up to 50% (r=0.465) in patients with diabetes mellitus, was found to be of medium strength. The patients with diabetes and CKD, myocardial infarction developed 79% more often than in patients without diabetes (p<0.05). Thus, immunogenic lipid markers of atherosclerosis can be considered both as mechanical factors of atherogenesis and diagnostic and prognostic characteristics in type 2 diabetic patients with impaired renal function and chronic renal insufficiency.
The conclusion. Accelerated development of atherosclerosis with diabetes and CKD, confirmed with the help of duplex scan of brachiocephalic arteries, may be associated with an increase in the level of modified low density lipoprotein.
Keywords: type 2 diabetes mellitus, program hemodialysis, atherosclerosis, modified low density lipoprotein, lipoprotein-containing circulating immune complexes.
Материалы и методы. Обследован 81 пациент с ХБП (50 мужчин / 31 женщина), получавших лечение ПГ, из них 36 (17/19) – с СД 2-го типа, 45 (33/12) – без СД 2-го типа. Определяли уровни общего холестерина (ОХС), триглицеридов (ТГ) и десиалированного апоВ-100 в плазме крови и ЦИК-ЛПНП. Для оценки степени развития атеросклероза использовали цветное дуплексное сканирование брахиоцефальных артерий (ЦДС БЦА) с определением толщины интимо-медиального комплекса (ИМК).
Результаты и обсуждение. Пациенты с СД 2-го типа имели высокие значения ОХС, ТГ (p<0,05). ЦДС БЦА показал увеличение толщины ИМК у всех пациентов, леченных ПГ, однако у больных СД толщина оказалась больше на 13% (p<0,05). У больных СД 2-го типа превалируют бляшки со стенозом до 50%, по сравнению с пациентами без СД (p<0,05). У пациентов с СД 2-го типа выявлен повышенный уровень цмЛПНП и ЦИК-ЛПНП в сравнении с пациентами без СД, получающими ПГ. Частота встречаемости достоверно выше для десиалированного апоВ-100 на 46% у больных с СД на гемодиализе по сравнению без СД (p<0,05). Отмечено повышение уровня ЦИК-ЛПНП на 39% (p<0,05) у пациентов с СД 2-го типа, по сравнению с больными без СД на фоне ПГ. Установлена средней силы корреляционная связь между десиалированным апоВ-100 и параметрами ЦДС БЦА (r=0,325), а также между уровнем ХС и наличием стенозов до 50% (r=0,465) у больных СД 2-го типа. Выявлено, что у пациентов с СД, получающих ПГ, острый инфаркт миокарда развивался на 79% чаще, чем у пациентов без СД (p<0,05).
Заключение. Ускоренное развитие атеросклероза при СД 2-го типа и ХБП, подтвержденное при помощи ЦДС БЦА, может быть связано с повышением уровня атерогенных цмЛПНП.
Ключевые слова: сахарный диабет 2-го типа, программный гемодиализ, атеросклероз, модифицированные липопротеиды низкой плотности, липопротеидсодержащие циркулирующие иммунные комплексы.
________________________________________________
Materials and methods. We examined 81 patients with CKD (50 men / 31 women) treated with program hemodialysis, of which 36 (17/19) with type 2 diabetes mellitus, 45 (33/12) non-diabetic patients. The levels of total cholesterol, triglycerides and desialylated apoB-100 in blood plasma and lipoprotein-containing circulating immune complexes. A color duplex scan of brachiocephalic arteries was used to assess the extent of development of atherosclerosis with the determination of the thickness of the intima–medial complex.
Results and discussion. Patients with diabetes had high values of total cholesterol, triglycerides (p<0.05). Duplex scan of brachiocephalic arteries showed an increase in the thickness of intima-medial complex in all patients for program hemodialysis, however, in patients with diabetes, the thickness was 13% higher (p<0.05). In patients with diabetes, plaques with stenosis up to 50% prevail, compared with non-diabetic patients, p<0.05. The incidence was significantly higher for desialized apoB-100 by 46% in patients with diabetes on hemodialysis compared non-diabetic patients (p<0.05). An increase in the level of lipoprotein-containing circulating immune complexes by 39%, (p<0.05) in patients with diabetes mellitus was observed, compared with patients non-diabetic patients. The correlation between desialized apoB-100 and duplex scan of brachiocephalic arteries parameters (r=0.325), as well as between the cholesterol level and stenosis up to 50% (r=0.465) in patients with diabetes mellitus, was found to be of medium strength. The patients with diabetes and CKD, myocardial infarction developed 79% more often than in patients without diabetes (p<0.05). Thus, immunogenic lipid markers of atherosclerosis can be considered both as mechanical factors of atherogenesis and diagnostic and prognostic characteristics in type 2 diabetic patients with impaired renal function and chronic renal insufficiency.
The conclusion. Accelerated development of atherosclerosis with diabetes and CKD, confirmed with the help of duplex scan of brachiocephalic arteries, may be associated with an increase in the level of modified low density lipoprotein.
Keywords: type 2 diabetes mellitus, program hemodialysis, atherosclerosis, modified low density lipoprotein, lipoprotein-containing circulating immune complexes.
Список литературы
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17. Lovre D, Shah S, Sihota A, Fonseca VA. Managing diabetes and cardiovascular risk in chronic kidney disease patients. Endocrinol Metab Clin North Am. 2018;47:237-257. doi: 10.1016/j.ecl.2017.10.006
18. Winocour PH. Diabetes and chronic kidney disease: an increasingly common multi-morbid disease in need of a paradigm shift in care. Diabet Med. 2018;35:300-305. doi: 10.1111/dme.13564
19. Burut DF, Karim Y. The role of immune complexes in atherogenesis. Angiology. 2010;61(7):679-689. doi: 10.1177/0003319710366124
20. Virella G, Lopes-Virella MF. The pathogenic role of the adaptive immune response to modified LDL in diabetes. Front Endocrinol (Lausanne). 2012;3:76. doi: 10.3389/fendo.2012.00076
21. Lindgren FT. Preparative ultracentrifugal laboratory procedures and suggestions for lipoprotein analysis. In: Perkins ED, ed. Analysis of lipids and lipoproteins. New York: American Oil Chemical Society; 1975. P. 205-224.
22. Tertov VV, Sobenin IA, Tonevitsky AG, Orekhov AN, Smirnov VN. Isolation of atherogenic modified (desialylated) low density lipoprotein from blood of atherosclerotic patients: separation from native lipoprotein by affinity chromatography. Biochem Biophys Res Commun. 1990;167(3):1122-1127. doi: 10.1016/0006-291x(90)90639-5
23. Sobenin IA, Tertov VV, Koschinsky T, Bunting CE, Slavina ES, Dedov II, Orekhov AN. Modified low density lipoprotein from diabetic patients causes cholesterol accumulation in human intimal aortic cells. Atherosclerosis. 1993;100:41-54. doi: 10.1016/0021-9150(93)90066-4
24. Campbell DJ, Neal BC, Chalmers JP, Colman SA, Jenkins AJ, Kemp BE, et al. Low-density lipoprotein particles and risk of intracerebral haemorrhage in subjects with cerebrovascular disease. Eur J Cardiovasc Prev Rehabil. 2007;14(3):413-418. doi: 10.1097/hjr.0b013e328010f275
25. Tertov VV, Mukhin DN, Mikhallenko IA. Modification of low density lipoprotein by desialylation causes lipid accumulation in cultured cells: discovery of desialylated lipoprotein with altered cellular metabolism in the blood of atherosclerotic patients. Biochem Biophys Res Commun. 1989;162:206-211. doi: 10.1016/0006-291x(89)91982-7
26. Lopes-Virella MF, Klein RL, Lyons TJ, Stevenson HC, Witztum JL. Glycosylation of low-density lipoprotein enhances cholesteryl ester synthesis in human monocytederived macrophages. Diabetes. 1988;37(5):550-557. doi: 10.2337/diabetes.37.5.550
27. Tanaka M, Abe Y, Furukado S, Miwa K, Sakaguchi M, Sakoda S, Kitagawa K. Chronic Kidney Disease and Carotid Atherosclerosis. Stroke Cerebrovasc Dis. 2012;21(1):47-51. doi: 10.1016/j.jstrokecerebrovasdis.2010.03.018
28. Dahlen GH. Lp(a) lipoprotein in cardiovascular disease. Atherosclerosis. 1994;108:111-126. doi: 10.1016/0021-9150(94)90106-6
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2. [Zubkova ST. Risk factors for atherosclerosis in patients with diabetes mellitus. Zdorov'e Ukrainy = Health of Ukraine. 2013;(2):24-25 (In Russ.)].
3. Souvik S, Stephen M. Risk Factors for Progression of Aortic Atheroma in Stroke and Transient Ischemic Attack Patients. Stroke. 2002;33:930-935. doi: 10.1161/01.STR.0000014210.99337.D7
4. [Ots M, Pekhter U. Premature Atherosclerosis in Chronic Renal Failure. Nefrologiya i Dializ = Nephrology and Dialysis. 2002;4(3):210-213 (In Russ.)].
5. Lehto S, Niskanen L, Ronnemaa T, Laakso M. Medial artery calcification in non insulin dependent diabetes mellitus. Arterioscler Thromb Vasc Biol. 1996;16:978-983. doi: 10.1161/01.ATV.16.8.978
6. Kannel WB, Larson M. Long-term epidemiologic prediction of coronary disease. The Framingham experience. Cardiology. 1993;(82):137-152. doi: 10.1159/000175864
7. Griffith RL, Virella GT, Stevenson HC, Lopes-Virella MF. Low density lipoprotein metabolism by human macrophages activated with low density lipoprotein immune complexes. A possible mechanism of foam cell formation. J Exp Med. 1988;168(3):1041-1059. doi: 10.1084/jem.168.3.1041
8. Zakiev ER, Sobenin IA, Sukhorukov VN, Myasoedova VA, Ivanova EA, Orekhov AN. Carbohydrate composition of circulating multiple-modified low-density lipoprotein. Vasc Health Risk Manag. 2016;12:379-385. doi: 10.2147/vhrm.s112948
9. Zakiev ER, Sukhorukov VN, Melnichenko AA, Sobenin IA, Ivanova EA, Orekhov AN. Lipid composition of circulating multiple-modified low density lipoprotein. Lipids Health Dis. 2016;15:134. doi: 10.1186/s12944-016-0308-2
10. Sobenin IA, Tertov VV, Orekhov AN. Atherogenic modified LDL in diabetes. Diabetes. 1996;45(3):S35-S39. doi: 10.2337/diab.45.3.s35
11. Palinski W, Rosenfeld ME, Yla-Herttuala S, et al. Low density lipoprotein undergoes oxidative modification in vivo. Proc Nat Acad Sci U. S. A. 1989;86(4):1372-1376. doi: 10.1073/pnas.86.4.1372
12. Piarulli F, Lapolla A, Sartore G. Autoantibodies Against Oxidized LDLs and Atherosclerosis in Type 2 Diabetes. Diabetes Care. 2005;28:653-657. doi: 10.2337/diacare.28.3.653
13. Orekhov AN, Bobryshev YV, Sobenin IA, Melnichenko AA, Chistiakov DA. Modified low density lipoprotein and lipoprotein-containing circulating immune complexes as diagnostic and prognostic biomarkers of atherosclerosis and type 1 diabetes macrovascular disease. Int J Mol Sci. 2014;15:12807-12841. doi: 10.3390/ijms150712807
14. Virella G, Lopes-Virella MF. The role of the immune system in the pathogenesis of diabetic complications. Front Endocrinol (Lausanne). 2014;5:126. doi: 10.3389/fendo.2014.00126
15. Hunt KJ, Baker N, Cleary P, Backlund JY, Lyons T, Jenkins A, Virella G, Lopes-Virella MF. Oxidized LDL and AGE-LDL in circulating immune complexes strongly predict progression of carotid artery IMT in type 1 diabetes. Atherosclerosis. 2013;231:315-322. doi: 10.1016/j.atherosclerosis.2013.09.027
16. Ketelhuth DF, Hansson GK. Modulation of autoimmunity and atherosclerosis – common targets and promising translational approaches against disease. Circ J. 2015;79(5):924-933. doi: 10.1253/circj.cj-15-0167
17. Lovre D, Shah S, Sihota A, Fonseca VA. Managing diabetes and cardiovascular risk in chronic kidney disease patients. Endocrinol Metab Clin North Am. 2018;47:237-257. doi: 10.1016/j.ecl.2017.10.006
18. Winocour PH. Diabetes and chronic kidney disease: an increasingly common multi-morbid disease in need of a paradigm shift in care. Diabet Med. 2018;35:300-305. doi: 10.1111/dme.13564
19. Burut DF, Karim Y. The role of immune complexes in atherogenesis. Angiology. 2010;61(7):679-689. doi: 10.1177/0003319710366124
20. Virella G, Lopes-Virella MF. The pathogenic role of the adaptive immune response to modified LDL in diabetes. Front Endocrinol (Lausanne). 2012;3:76. doi: 10.3389/fendo.2012.00076
21. Lindgren FT. Preparative ultracentrifugal laboratory procedures and suggestions for lipoprotein analysis. In: Perkins ED, ed. Analysis of lipids and lipoproteins. New York: American Oil Chemical Society; 1975. P. 205-224.
22. Tertov VV, Sobenin IA, Tonevitsky AG, Orekhov AN, Smirnov VN. Isolation of atherogenic modified (desialylated) low density lipoprotein from blood of atherosclerotic patients: separation from native lipoprotein by affinity chromatography. Biochem Biophys Res Commun. 1990;167(3):1122-1127. doi: 10.1016/0006-291x(90)90639-5
23. Sobenin IA, Tertov VV, Koschinsky T, Bunting CE, Slavina ES, Dedov II, Orekhov AN. Modified low density lipoprotein from diabetic patients causes cholesterol accumulation in human intimal aortic cells. Atherosclerosis. 1993;100:41-54. doi: 10.1016/0021-9150(93)90066-4
24. Campbell DJ, Neal BC, Chalmers JP, Colman SA, Jenkins AJ, Kemp BE, et al. Low-density lipoprotein particles and risk of intracerebral haemorrhage in subjects with cerebrovascular disease. Eur J Cardiovasc Prev Rehabil. 2007;14(3):413-418. doi: 10.1097/hjr.0b013e328010f275
25. Tertov VV, Mukhin DN, Mikhallenko IA. Modification of low density lipoprotein by desialylation causes lipid accumulation in cultured cells: discovery of desialylated lipoprotein with altered cellular metabolism in the blood of atherosclerotic patients. Biochem Biophys Res Commun. 1989;162:206-211. doi: 10.1016/0006-291x(89)91982-7
26. Lopes-Virella MF, Klein RL, Lyons TJ, Stevenson HC, Witztum JL. Glycosylation of low-density lipoprotein enhances cholesteryl ester synthesis in human monocytederived macrophages. Diabetes. 1988;37(5):550-557. doi: 10.2337/diabetes.37.5.550
27. Tanaka M, Abe Y, Furukado S, Miwa K, Sakaguchi M, Sakoda S, Kitagawa K. Chronic Kidney Disease and Carotid Atherosclerosis. Stroke Cerebrovasc Dis. 2012;21(1):47-51. doi: 10.1016/j.jstrokecerebrovasdis.2010.03.018
28. Dahlen GH. Lp(a) lipoprotein in cardiovascular disease. Atherosclerosis. 1994;108:111-126. doi: 10.1016/0021-9150(94)90106-6
29. Fowler MJ. Microvascular and macrovascular complications of diabetes. Clin Diabetes. 2008;26(2):77-82. doi: 10.2337/diaclin.26.2.77
30. Kato A, Takita T, Maruyama Y, Kumagai H, Hishida A. Impact of carotid atherosclerosis on long-term mortality in chronic hemodialysis patients. Kidney Int. 2003;64(4):1472-1479. doi: 10.1046/j.1523-1755.2003.00205.x
31. Bucala R, Makita Z, Vega G, Grundy S, Koschinsky T. Modification of low density lipoprotein by advanced glycation end products contributes to the dyslipidemia of diabetes and renal insufficiency. Proc Nat Acad Sci. 1994;91(20):9441-9445. doi: 10.1073/pnas.91.20.9441
32. Klimov AN, Denisenko AD, Popov AV. Lipoproteinantibody immune complexes their catabolism and role in foam cell formation. Atherosclerosis. 1985;58(1-3):1-15. doi: 10.1016/0021-9150(85)90051-6
33. [Babintseva JD, Sergeeva AM, Karagodin VP, Orekhov AN. Atherogenesis in humans – the clinical aspects of circulating immune complexes. Klinicheskaya Meditsina = Clinical Medicine. 2016;94(5):325-332 (In Russ.)]. doi: 10.18821/0023-2149-2016-94-5-325-332
34. Gonen B, Fallon JJ, Baker SA. Immunogenicity of malondialdehyde-modified low density lipoproteins: studies with monoclonal antibodies. Atherosclerosis. 1987;65:265-272. doi: 10.1016/0021-9150(87)90042-6
35. Numano F, Tanaka A, Makita T, Kishi Y. Glycated lipoprotein and atherosclerosis. Ann NY Acad Sci. 1997;811:100-114. doi: 10.1111/j. 1749-6632.1997.tb51993.x
36. Galle J, Wanner С. Modification of Lipoproteins in Uremia: Oxidation, Glycation and Carbamoylation. Mineral Electrol Metab. 1999;25:263-268.
2. Зубкова С.Т. Факторы риска атеросклероза у больных с сахарным диабетом. Здоровье Украины. 2013;(2):24-25 [Zubkova ST. Risk factors for atherosclerosis in patients with diabetes mellitus. Zdorov'e Ukrainy = Health of Ukraine. 2013;(2):24-25 (In Russ.)].
3. Souvik S, Stephen M. Risk Factors for Progression of Aortic Atheroma in Stroke and Transient Ischemic Attack Patients. Stroke. 2002;33:930-935. doi: 10.1161/01.STR.0000014210.99337.D7
4. Отс М., Пехтер У. Преждевременный атеросклероз при хронической почечной недостаточности. Нефрология и диализ. 2002;4(3):210-213 [Ots M, Pekhter U. Premature Atherosclerosis in Chronic Renal Failure. Nefrologiya i Dializ = Nephrology and Dialysis. 2002;4(3):210-213 (In Russ.)].
5. Lehto S, Niskanen L, Ronnemaa T, Laakso M. Medial artery calcification in non insulin dependent diabetes mellitus. Arterioscler Thromb Vasc Biol. 1996;16:978-983. doi: 10.1161/01.ATV.16.8.978
6. Kannel WB, Larson M. Long-term epidemiologic prediction of coronary disease. The Framingham experience. Cardiology. 1993;(82):137-152. doi: 10.1159/000175864
7. Griffith RL, Virella GT, Stevenson HC, Lopes-Virella MF. Low density lipoprotein metabolism by human macrophages activated with low density lipoprotein immune complexes. A possible mechanism of foam cell formation. J Exp Med. 1988;168(3):1041-1059. doi: 10.1084/jem.168.3.1041
8. Zakiev ER, Sobenin IA, Sukhorukov VN, Myasoedova VA, Ivanova EA, Orekhov AN. Carbohydrate composition of circulating multiple-modified low-density lipoprotein. Vasc Health Risk Manag. 2016;12:379-385. doi: 10.2147/vhrm.s112948
9. Zakiev ER, Sukhorukov VN, Melnichenko AA, Sobenin IA, Ivanova EA, Orekhov AN. Lipid composition of circulating multiple-modified low density lipoprotein. Lipids Health Dis. 2016;15:134. doi: 10.1186/s12944-016-0308-2
10. Sobenin IA, Tertov VV, Orekhov AN. Atherogenic modified LDL in diabetes. Diabetes. 1996;45(3):S35-S39. doi: 10.2337/diab.45.3.s35
11. Palinski W, Rosenfeld ME, Yla-Herttuala S, et al. Low density lipoprotein undergoes oxidative modification in vivo. Proc Nat Acad Sci U. S. A. 1989;86(4):1372-1376. doi: 10.1073/pnas.86.4.1372
12. Piarulli F, Lapolla A, Sartore G. Autoantibodies Against Oxidized LDLs and Atherosclerosis in Type 2 Diabetes. Diabetes Care. 2005;28:653-657. doi: 10.2337/diacare.28.3.653
13. Orekhov AN, Bobryshev YV, Sobenin IA, Melnichenko AA, Chistiakov DA. Modified low density lipoprotein and lipoprotein-containing circulating immune complexes as diagnostic and prognostic biomarkers of atherosclerosis and type 1 diabetes macrovascular disease. Int J Mol Sci. 2014;15:12807-12841. doi: 10.3390/ijms150712807
14. Virella G, Lopes-Virella MF. The role of the immune system in the pathogenesis of diabetic complications. Front Endocrinol (Lausanne). 2014;5:126. doi: 10.3389/fendo.2014.00126
15. Hunt KJ, Baker N, Cleary P, Backlund JY, Lyons T, Jenkins A, Virella G, Lopes-Virella MF. Oxidized LDL and AGE-LDL in circulating immune complexes strongly predict progression of carotid artery IMT in type 1 diabetes. Atherosclerosis. 2013;231:315-322. doi: 10.1016/j.atherosclerosis.2013.09.027
16. Ketelhuth DF, Hansson GK. Modulation of autoimmunity and atherosclerosis – common targets and promising translational approaches against disease. Circ J. 2015;79(5):924-933. doi: 10.1253/circj.cj-15-0167
17. Lovre D, Shah S, Sihota A, Fonseca VA. Managing diabetes and cardiovascular risk in chronic kidney disease patients. Endocrinol Metab Clin North Am. 2018;47:237-257. doi: 10.1016/j.ecl.2017.10.006
18. Winocour PH. Diabetes and chronic kidney disease: an increasingly common multi-morbid disease in need of a paradigm shift in care. Diabet Med. 2018;35:300-305. doi: 10.1111/dme.13564
19. Burut DF, Karim Y. The role of immune complexes in atherogenesis. Angiology. 2010;61(7):679-689. doi: 10.1177/0003319710366124
20. Virella G, Lopes-Virella MF. The pathogenic role of the adaptive immune response to modified LDL in diabetes. Front Endocrinol (Lausanne). 2012;3:76. doi: 10.3389/fendo.2012.00076
21. Lindgren FT. Preparative ultracentrifugal laboratory procedures and suggestions for lipoprotein analysis. In: Perkins ED, ed. Analysis of lipids and lipoproteins. New York: American Oil Chemical Society; 1975. P. 205-224.
22. Tertov VV, Sobenin IA, Tonevitsky AG, Orekhov AN, Smirnov VN. Isolation of atherogenic modified (desialylated) low density lipoprotein from blood of atherosclerotic patients: separation from native lipoprotein by affinity chromatography. Biochem Biophys Res Commun. 1990;167(3):1122-1127. doi: 10.1016/0006-291x(90)90639-5
23. Sobenin IA, Tertov VV, Koschinsky T, Bunting CE, Slavina ES, Dedov II, Orekhov AN. Modified low density lipoprotein from diabetic patients causes cholesterol accumulation in human intimal aortic cells. Atherosclerosis. 1993;100:41-54. doi: 10.1016/0021-9150(93)90066-4
24. Campbell DJ, Neal BC, Chalmers JP, Colman SA, Jenkins AJ, Kemp BE, et al. Low-density lipoprotein particles and risk of intracerebral haemorrhage in subjects with cerebrovascular disease. Eur J Cardiovasc Prev Rehabil. 2007;14(3):413-418. doi: 10.1097/hjr.0b013e328010f275
25. Tertov VV, Mukhin DN, Mikhallenko IA. Modification of low density lipoprotein by desialylation causes lipid accumulation in cultured cells: discovery of desialylated lipoprotein with altered cellular metabolism in the blood of atherosclerotic patients. Biochem Biophys Res Commun. 1989;162:206-211. doi: 10.1016/0006-291x(89)91982-7
26. Lopes-Virella MF, Klein RL, Lyons TJ, Stevenson HC, Witztum JL. Glycosylation of low-density lipoprotein enhances cholesteryl ester synthesis in human monocytederived macrophages. Diabetes. 1988;37(5):550-557. doi: 10.2337/diabetes.37.5.550
27. Tanaka M, Abe Y, Furukado S, Miwa K, Sakaguchi M, Sakoda S, Kitagawa K. Chronic Kidney Disease and Carotid Atherosclerosis. Stroke Cerebrovasc Dis. 2012;21(1):47-51. doi: 10.1016/j.jstrokecerebrovasdis.2010.03.018
28. Dahlen GH. Lp(a) lipoprotein in cardiovascular disease. Atherosclerosis. 1994;108:111-126. doi: 10.1016/0021-9150(94)90106-6
29. Fowler MJ. Microvascular and macrovascular complications of diabetes. Clin Diabetes. 2008;26(2):77-82. doi: 10.2337/diaclin.26.2.77
30. Kato A, Takita T, Maruyama Y, Kumagai H, Hishida A. Impact of carotid atherosclerosis on long-term mortality in chronic hemodialysis patients. Kidney Int. 2003;64(4):1472-1479. doi: 10.1046/j.1523-1755.2003.00205.x
31. Bucala R, Makita Z, Vega G, Grundy S, Koschinsky T. Modification of low density lipoprotein by advanced glycation end products contributes to the dyslipidemia of diabetes and renal insufficiency. Proc Nat Acad Sci. 1994;91(20):9441-9445. doi: 10.1073/pnas.91.20.9441
32. Klimov AN, Denisenko AD, Popov AV. Lipoproteinantibody immune complexes their catabolism and role in foam cell formation. Atherosclerosis. 1985;58(1-3):1-15. doi: 10.1016/0021-9150(85)90051-6
33. Бабинцева Я.Д., Сергеева А.М., Карагодин В.П., Орехов А.Н. Атерогенез у человека – клинические аспекты циркулирующих иммунных комплексов. Клиническая медицина. 2016;94(5):325-332 [Babintseva JD, Sergeeva AM, Karagodin VP, Orekhov AN. Atherogenesis in humans – the clinical aspects of circulating immune complexes. Klinicheskaya Meditsina = Clinical Medicine. 2016;94(5):325-332 (In Russ.)]. doi: 10.18821/0023-2149-2016-94-5-325-332
34. Gonen B, Fallon JJ, Baker SA. Immunogenicity of malondialdehyde-modified low density lipoproteins: studies with monoclonal antibodies. Atherosclerosis. 1987;65:265-272. doi: 10.1016/0021-9150(87)90042-6
35. Numano F, Tanaka A, Makita T, Kishi Y. Glycated lipoprotein and atherosclerosis. Ann NY Acad Sci. 1997;811:100-114. doi: 10.1111/j. 1749-6632.1997.tb51993.x
36. Galle J, Wanner С. Modification of Lipoproteins in Uremia: Oxidation, Glycation and Carbamoylation. Mineral Electrol Metab. 1999;25:263-268.
________________________________________________
2. [Zubkova ST. Risk factors for atherosclerosis in patients with diabetes mellitus. Zdorov'e Ukrainy = Health of Ukraine. 2013;(2):24-25 (In Russ.)].
3. Souvik S, Stephen M. Risk Factors for Progression of Aortic Atheroma in Stroke and Transient Ischemic Attack Patients. Stroke. 2002;33:930-935. doi: 10.1161/01.STR.0000014210.99337.D7
4. [Ots M, Pekhter U. Premature Atherosclerosis in Chronic Renal Failure. Nefrologiya i Dializ = Nephrology and Dialysis. 2002;4(3):210-213 (In Russ.)].
5. Lehto S, Niskanen L, Ronnemaa T, Laakso M. Medial artery calcification in non insulin dependent diabetes mellitus. Arterioscler Thromb Vasc Biol. 1996;16:978-983. doi: 10.1161/01.ATV.16.8.978
6. Kannel WB, Larson M. Long-term epidemiologic prediction of coronary disease. The Framingham experience. Cardiology. 1993;(82):137-152. doi: 10.1159/000175864
7. Griffith RL, Virella GT, Stevenson HC, Lopes-Virella MF. Low density lipoprotein metabolism by human macrophages activated with low density lipoprotein immune complexes. A possible mechanism of foam cell formation. J Exp Med. 1988;168(3):1041-1059. doi: 10.1084/jem.168.3.1041
8. Zakiev ER, Sobenin IA, Sukhorukov VN, Myasoedova VA, Ivanova EA, Orekhov AN. Carbohydrate composition of circulating multiple-modified low-density lipoprotein. Vasc Health Risk Manag. 2016;12:379-385. doi: 10.2147/vhrm.s112948
9. Zakiev ER, Sukhorukov VN, Melnichenko AA, Sobenin IA, Ivanova EA, Orekhov AN. Lipid composition of circulating multiple-modified low density lipoprotein. Lipids Health Dis. 2016;15:134. doi: 10.1186/s12944-016-0308-2
10. Sobenin IA, Tertov VV, Orekhov AN. Atherogenic modified LDL in diabetes. Diabetes. 1996;45(3):S35-S39. doi: 10.2337/diab.45.3.s35
11. Palinski W, Rosenfeld ME, Yla-Herttuala S, et al. Low density lipoprotein undergoes oxidative modification in vivo. Proc Nat Acad Sci U. S. A. 1989;86(4):1372-1376. doi: 10.1073/pnas.86.4.1372
12. Piarulli F, Lapolla A, Sartore G. Autoantibodies Against Oxidized LDLs and Atherosclerosis in Type 2 Diabetes. Diabetes Care. 2005;28:653-657. doi: 10.2337/diacare.28.3.653
13. Orekhov AN, Bobryshev YV, Sobenin IA, Melnichenko AA, Chistiakov DA. Modified low density lipoprotein and lipoprotein-containing circulating immune complexes as diagnostic and prognostic biomarkers of atherosclerosis and type 1 diabetes macrovascular disease. Int J Mol Sci. 2014;15:12807-12841. doi: 10.3390/ijms150712807
14. Virella G, Lopes-Virella MF. The role of the immune system in the pathogenesis of diabetic complications. Front Endocrinol (Lausanne). 2014;5:126. doi: 10.3389/fendo.2014.00126
15. Hunt KJ, Baker N, Cleary P, Backlund JY, Lyons T, Jenkins A, Virella G, Lopes-Virella MF. Oxidized LDL and AGE-LDL in circulating immune complexes strongly predict progression of carotid artery IMT in type 1 diabetes. Atherosclerosis. 2013;231:315-322. doi: 10.1016/j.atherosclerosis.2013.09.027
16. Ketelhuth DF, Hansson GK. Modulation of autoimmunity and atherosclerosis – common targets and promising translational approaches against disease. Circ J. 2015;79(5):924-933. doi: 10.1253/circj.cj-15-0167
17. Lovre D, Shah S, Sihota A, Fonseca VA. Managing diabetes and cardiovascular risk in chronic kidney disease patients. Endocrinol Metab Clin North Am. 2018;47:237-257. doi: 10.1016/j.ecl.2017.10.006
18. Winocour PH. Diabetes and chronic kidney disease: an increasingly common multi-morbid disease in need of a paradigm shift in care. Diabet Med. 2018;35:300-305. doi: 10.1111/dme.13564
19. Burut DF, Karim Y. The role of immune complexes in atherogenesis. Angiology. 2010;61(7):679-689. doi: 10.1177/0003319710366124
20. Virella G, Lopes-Virella MF. The pathogenic role of the adaptive immune response to modified LDL in diabetes. Front Endocrinol (Lausanne). 2012;3:76. doi: 10.3389/fendo.2012.00076
21. Lindgren FT. Preparative ultracentrifugal laboratory procedures and suggestions for lipoprotein analysis. In: Perkins ED, ed. Analysis of lipids and lipoproteins. New York: American Oil Chemical Society; 1975. P. 205-224.
22. Tertov VV, Sobenin IA, Tonevitsky AG, Orekhov AN, Smirnov VN. Isolation of atherogenic modified (desialylated) low density lipoprotein from blood of atherosclerotic patients: separation from native lipoprotein by affinity chromatography. Biochem Biophys Res Commun. 1990;167(3):1122-1127. doi: 10.1016/0006-291x(90)90639-5
23. Sobenin IA, Tertov VV, Koschinsky T, Bunting CE, Slavina ES, Dedov II, Orekhov AN. Modified low density lipoprotein from diabetic patients causes cholesterol accumulation in human intimal aortic cells. Atherosclerosis. 1993;100:41-54. doi: 10.1016/0021-9150(93)90066-4
24. Campbell DJ, Neal BC, Chalmers JP, Colman SA, Jenkins AJ, Kemp BE, et al. Low-density lipoprotein particles and risk of intracerebral haemorrhage in subjects with cerebrovascular disease. Eur J Cardiovasc Prev Rehabil. 2007;14(3):413-418. doi: 10.1097/hjr.0b013e328010f275
25. Tertov VV, Mukhin DN, Mikhallenko IA. Modification of low density lipoprotein by desialylation causes lipid accumulation in cultured cells: discovery of desialylated lipoprotein with altered cellular metabolism in the blood of atherosclerotic patients. Biochem Biophys Res Commun. 1989;162:206-211. doi: 10.1016/0006-291x(89)91982-7
26. Lopes-Virella MF, Klein RL, Lyons TJ, Stevenson HC, Witztum JL. Glycosylation of low-density lipoprotein enhances cholesteryl ester synthesis in human monocytederived macrophages. Diabetes. 1988;37(5):550-557. doi: 10.2337/diabetes.37.5.550
27. Tanaka M, Abe Y, Furukado S, Miwa K, Sakaguchi M, Sakoda S, Kitagawa K. Chronic Kidney Disease and Carotid Atherosclerosis. Stroke Cerebrovasc Dis. 2012;21(1):47-51. doi: 10.1016/j.jstrokecerebrovasdis.2010.03.018
28. Dahlen GH. Lp(a) lipoprotein in cardiovascular disease. Atherosclerosis. 1994;108:111-126. doi: 10.1016/0021-9150(94)90106-6
29. Fowler MJ. Microvascular and macrovascular complications of diabetes. Clin Diabetes. 2008;26(2):77-82. doi: 10.2337/diaclin.26.2.77
30. Kato A, Takita T, Maruyama Y, Kumagai H, Hishida A. Impact of carotid atherosclerosis on long-term mortality in chronic hemodialysis patients. Kidney Int. 2003;64(4):1472-1479. doi: 10.1046/j.1523-1755.2003.00205.x
31. Bucala R, Makita Z, Vega G, Grundy S, Koschinsky T. Modification of low density lipoprotein by advanced glycation end products contributes to the dyslipidemia of diabetes and renal insufficiency. Proc Nat Acad Sci. 1994;91(20):9441-9445. doi: 10.1073/pnas.91.20.9441
32. Klimov AN, Denisenko AD, Popov AV. Lipoproteinantibody immune complexes their catabolism and role in foam cell formation. Atherosclerosis. 1985;58(1-3):1-15. doi: 10.1016/0021-9150(85)90051-6
33. [Babintseva JD, Sergeeva AM, Karagodin VP, Orekhov AN. Atherogenesis in humans – the clinical aspects of circulating immune complexes. Klinicheskaya Meditsina = Clinical Medicine. 2016;94(5):325-332 (In Russ.)]. doi: 10.18821/0023-2149-2016-94-5-325-332
34. Gonen B, Fallon JJ, Baker SA. Immunogenicity of malondialdehyde-modified low density lipoproteins: studies with monoclonal antibodies. Atherosclerosis. 1987;65:265-272. doi: 10.1016/0021-9150(87)90042-6
35. Numano F, Tanaka A, Makita T, Kishi Y. Glycated lipoprotein and atherosclerosis. Ann NY Acad Sci. 1997;811:100-114. doi: 10.1111/j. 1749-6632.1997.tb51993.x
36. Galle J, Wanner С. Modification of Lipoproteins in Uremia: Oxidation, Glycation and Carbamoylation. Mineral Electrol Metab. 1999;25:263-268.
Авторы
Т.В. Арчакова 1, Л.В. Недосугова 1, Н.А. Никитина 2, А.А. Мельниченко 2, И.А. Собенин 2
1 ФГАОУ «ВО Первый Московский медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия;
2 ФГБУ «Национальный медицинский исследовательский центр кардиологии» Минздрава России, Москва, Россия
1 I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Healht of Russia, Moscow, Russia;
2 National Medical Research Center of Cardiology, Ministry of Healht of Russia, Moscow, Russia
1 ФГАОУ «ВО Первый Московский медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия;
2 ФГБУ «Национальный медицинский исследовательский центр кардиологии» Минздрава России, Москва, Россия
________________________________________________
1 I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Healht of Russia, Moscow, Russia;
2 National Medical Research Center of Cardiology, Ministry of Healht of Russia, Moscow, Russia
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