Plasma dyslipidemia: pathogenesis and diagnostic value. Literature review

Abstract

This review discusses the problem of diagnostics of atherosclerosis from the standpoint of the need of developing new approaches and principles for more effective detection of this disease at the early stages of its course in the humans. The insufficiently studied basic stages and mechanisms of lipid metabolism are indicated, which in the future may have diagnostic value. The lipid composition of blood plasma and its fractions, which are associated with a high risk of the occurrence and development of cardiovascular disease (CVD) is assessed. The determining of the role of cholesterol, lipoproteins and apolipoproteins in the pathogenesis of atherosclerosis, a wide variability of the atherogenic lipid profile and its direct relationship with calcium metabolism in atherosclerotic damage of the vascular wall is accentuated. It is shown that the basis of dyslipidemia and civilization diseases (atherosclerosis, obesity, diabetes mellitus) is a disorder of the mechanisms of neurohumoral regulation of lipid metabolism. The immunological mechanisms of the pathogenesis of atherosclerotic process and the marker signs that identify this process are discussed in details. A generalized scheme of peroxidation of blood plasma lipoproteins and the subsequent molecular-cellular stages of the formation of atherosclerotic plaques in the intima of the vascular wall is presented. The current modern methods of diagnosing dyslipidemia are briefly described and the lipid-lowering effects of certain drugs are noted, a forecast is given for the creation of new, more effective statins. In conclusion, the work confirms the importance of studying the qualitative composition of lipids and the expansion of physico-chemical and molecular genetic diagnostic methods for studying metabolism.

Keywords

Cholesterol / lipoproteins / atherosclerosis / cardiovascular disease / diagnostics

References

[1] Kovaleva Yu.V., Pyrkh O.V. Changes in the biochemical parameters of blood serum with atherosclerosis of blood vessels of various localization. Actual scientific research in the modern world 2018; 11–6 (43): 20–23 (in Russian).

[2] Ковалева Ю.В., Пырх О.В. Изменения биохимических показателей сыворотки крови при атеросклерозе сосудов различной локализации. Актуальные научные исследования в современном мире 2018; 11–6 (43): 20–23.

[3] Pshibieva S.V., Sizhazheva A.M., Shogenova R.S., Khulaev I.V. The use of various laboratory methods in the diagnosis of atherosclerosis of coronary heart disease. Modern problems of science and education 2016; 2: 53 (in Russian).

[4] Пшибиева С.В., Сижажева А.М., Шогенова Р.С., Хулаев И.В. Применение различных лабораторных методов при диагностике атеросклероза ишемической болезни сердца. Современные проблемы науки и образования 2016; 2: 53.

[5] Ohukainen P., Kuusisto S. Kettunen J. et al. Data-driven multivariate population subgrouping via lipoprotein phenotypes versus apolipoprotein B in the risk assessment of coronary heart disease. Atherosclerosis 2019; 294: 10–15. DOI: 10.1016/j.atherosclerosis. 2019.12.009.

[6] Ohukainen P., Kuusisto S., Kettunen J. et al. Data-driven multivariate population subgrouping via lipoprotein phenotypes versus apolipoprotein B in the risk assessment of coronary heart disease. Atherosclerosis 2019; 294: 10–15. DOI: 10.1016/j.atherosclerosis.2019.12.009.

[7] Axmann M., Strobl W.M., Plochberger B., Stangl H. Cholesterol transfer at the plasma membrane. Atherosclerosis 2019; 290: 111–117. DOI: 10.1016/j.atherosclerosis.2019.09.022.

[8] Pašková U. Lipid profile and risks of cardiovascular diseases in conditions of rheumatoid arthritis. Ceska Slov Farm. 2019; 68 (6): 219–228.

[9] Pašková U. Lipid profile and risks of cardiovascular diseases in conditions of rheumatoid arthritis. Ceska Slov Farm 2019; 68 (6): 219–228.

[10] Ceglarek U., Dittrich J., Leopold J. et al. Free cholesterol, cholesterol precursor and plant sterol levels in atherosclerotic plaques are independently associated with symptomatic advanced carotid artery stenosis. Atherosclerosis 2019; 295: 18–24. DOI: 10.1016/j.atherosclerosis.2019.12.018.

[11] Krakowiak J., Raczkiewicz D., Wdowiak A. et al. Atherogenic lipid profile and health behaviours in women post-menopause working in agriculture. Ann Agric Environ Med. 2019; 26 (4): 585–591. DOI: 10.26444/ aaem/105391.

[12] Krakowiak J., Raczkiewicz D., Wdowiak A. et al. Atherogenic lipid profile and health behaviours in women post-menopause working in agriculture. Ann Agric Environ Med. 2019; 26 (4): 585–591. DOI: 10.26444/aaem/105391.

[13] Gavrilova N.E., Metelskaya V.A., Ozerova I.N. et al. Features of the subfraction spectrum of alipoprotein B-containing lipoproteins in patients with carotid and / or coronary atherosclerosis. Russian Journal of Cardiology 2016; 10 (138): 64–70. DOI: 10.15829/1560-4071-2016-10-64-70 (in Russian)

[14] Гаврилова Н.Е., Метельская В.А., Озерова И.Н. и др. Особенности субфракционного спектра алипопротеин В-содержащих липопротеинов у больных с каротидным и/или коронарным атеросклерозом. Российский кардиологический журнал 2016; 10 (138): 64–70. DOI: 10.15829/1560-4071-2016-10-64-70

[15] Mishlanov V.Yu., Vladimirsky V.E. Leukocyte and serum risk factors in patients with arteriosclerosis obliterans of the lower limb arteries. Modern problems of science and education 2015; 1–1: 1306 (in Russian).

[16] Мишланов В.Ю., Владимирский В.Е. Лейкоцитарные и сывороточные факторы риска у больных облитерирующим атеросклерозом артерий нижних конечностей. Современные проблемы науки и образования 2015; 1 (1): 1306.

[17] Voskresenskaya O.N., Zakharova N.B., Tarasova Yu.S., Tereshkina N.E. Biomarkers of endothelial dysfunction in chronic cerebral ischemia. Medical almanac 2018; 5 (56): 41–43 (in Russian).

[18] Воскресенская О.Н., Захарова Н.Б., Тарасова Ю.С., Терешкина Н.Е. Биомаркеры эндотелиальной дисфункции при хронической ишемии головного мозга. Медицинский альманах 2018; 5 (56): 41–43.

[19] Kashtanova E.V., Chernyakovsky A.M., Polonskaya Y.V. et al. Study of a complex of blood biomarkers in men with coronary atherosclerosis. Russian Journal of Cardiology 2016; 2 (130): 60–64. DOI: 10.15829/1560-4071-2016-2-60-64 (in Russian)

[20] Каштанова Е.В., Черняковский А.М., Полонская Я.В. и др. Исследование комплекса биомаркеров в крови у мужчин с коронарным атеросклерозом. Российский кардиологический журнал 2016; 2 (130): 60–64. DOI: 10.15829/1560-4071-2016-2-60-64

[21] Bonnefont-Rousselot D., Benouda L., Bittar R. et al. Antiatherogenic properties of high-density lipoproteins from arterial plasma are attenuated as compared to their counterparts of venous origin. Nutr Metab Cardiovasc Dis. 2020; 30 (1): 33–39. DOI: 10.1016/ j.numecd.2019.07.022.

[22] Bonnefont-Rousselot D., Benouda L., Bittar R. et al. Antiatherogenic properties of high-density lipoproteins from arterial plasma are attenuated as compared to their counterparts of venous origin. Nutr Metab Cardiovasc Dis. 2020; 30 (1): 33–39. DOI: 10.1016/j.numecd.2019.07.022.

[23] Vuorio A., Watts G.F., Schneider W.J., Tsimikas S. Familial hypercholesterolemia and elevated lipoprotein (a): double heritable risk and new therapeutic opportunities. J Intern Med. 2020; 287 (1): 2–18. DOI: 10.1111/joim.12981.

[24] Lin X., Racette S.B., Ma L. et al. Endogenous Cholesterol Excretion Is Negatively Associated With Carotid Intima-Media Thickness in Humans. Arterioscler Thromb Vasc Biol. 2017; 37 (12): 2364–2369. DOI: 10.1161/ATVBAHA.117.310081.

[25] Hoeke G., Kooijman S., Boon M.R. et al. Role of Brown Fat in Lipoprotein Metabolism and Atherosclerosis. Circ Res. 2016; 118 (1): 173–182. DOI: 10.1161/CIRCRESAHA.115.306647.

[26] de Lima-Junior J.C., Virginio VWM., Moura F.A. et al. Excess weight mediates changes in HDL pool that reduce cholesterol efflux capacity and increase antioxidant activity. Nutr Metab Cardiovasc Dis. 2020; 30 (2): 254–264. DOI: 10.1016/j.numecd.2019.09.017.

[27] De Lima-Junior J.C., Virginio VWM., Moura F.A. et al. Excess weight mediates changes in HDL pool that reduce cholesterol efflux capacity and increase antioxidant activity. Nutr Metab Cardiovasc Dis. 2020; 30 (2): 254–264. DOI: 10.1016/j.numecd.2019.09.017.

[28] Polonskaya Ya.V., Kashtanova E.V., Murashev I.S. and others. The relationship of the main indicators of calcium and lipid metabolism with atherosclerosis of the coronary arteries. Atherosclerosis and dyslipidemia 2015; 1 (18): 24–29 (in Russian).

[29] Полонская Я.В., Каштанова Е.В., Мурашев И.С. и др. Взаимосвязь основных показателей кальциевого и липидного обмена с атеросклерозом коронарных артерий. Атеросклероз и дислипидемии 2015; 1 (18): 24–29.

[30] Michurova M.S., Kalashnikov V.Yu., Smirnova O.M. et al. Importance of circulating progenitor cells with osteogenic activity in the development of atherosclerosis in patients with type 2 diabetes. Obesity and metabolism 2019; 16 (1): 62–69. DOI: https://doi.org/10.14341/ omet9831 (in Russian)

[31] Мичурова М.С., Калашников В.Ю., Смирнова О.М. и др. Значение циркулирующих прогениторных клеток с остеогенной активностью в развитии атеросклероза у больных сахарным диабетом 2-го типа. Ожирение и метаболизм 2019; 16 (1): 62–69. DOI: 10.14341/omet9831

[32] Sposito A.C., Zimetti F., Barreto J., Zanotti I. Lipid trafficking in cardiovascular disease. Adv Clin Chem. 2019; 92: 105–140. DOI: 10.1016/bs.acc.2019.04.002.

[33] Artemenkov A.A. Maladaptive neuropathological syndrome of blood vessel aging. Russian Journal of Cardiology 2019; 24 (9): 33–40. DOI: 10.15829/1560-4071-2019-9-33-40 (in Russian)

[34] Артеменков А.А. Дезадаптивный нейропатологический синдром старения кровеносных сосудов. Российский кардиологический журнал 2019; 24 (9): 33–40. DOI: 10.15829/1560-4071-2019-9-33-40

[35] Artemenkov AA. Disadaptive violations of the regulation of functions during aging. Advances in gerontology 2018; 31 (5): 696–706 (in Russian).

[36] Артеменков А.А. Дезадаптивные нарушения регуляции функций при старении. Успехи геронтологии 2018; 31 (5): 696–706.

[37] Kozlov V.A. Suppressor cells are the basis of atherosclerosis immunopathogenesis. Atherosclerosis 2015; 11 (2): 37–42 (in Russian).

[38] Козлов В.А. Клетки супрессоры – основа иммунопатогенеза атеросклероза. Атеросклероз 2015; 11 (2): 37–42.

[39] Shogenova M.Kh., Zhetisheva R.A., Karpov A.M. et al. Role of oxidative low-density lipoproteins and antibodies to them in the immuno-inflammatory process in atherosclerosis. Atherosclerosis and dyslipidemia 2015; (2): 17–21 (in Russian).

[40] Шогенова М.Х., Жетишева Р.А., Карпов А.М. и др. Роль окислительных липопротеинов низкой плотности и антител к ним в иммуно-воспалительном процессе при атеросклерозе. Атеросклероз и дислипидемии 2015; (2): 17–21.

[41] Belik I.V., Ivantsova A.A., Mamedova Z.E., Denisenko A.D. The content of antibodies to modified low density lipoproteins and their complexes in the blood of patients with various manifestations of atherosclerosis. Biomedical chemistry 2016; 62 (4): 471–475 (in Russian).

[42] Белик И.В., Иванцова А.А., Мамедова З.Э., Денисенко А.Д. Содержание антител к модифицированным липопротеинам низкой плотности и их комплексов в крови пациентов с различными проявлениями атеросклероза. Биомедицинская химия 2016; 62 (4): 471–475.

[43] Bernelot Moens S.J., Verweij S.L., Schnitzler J.G. et al. Remnant Cholesterol Elicits Arterial Wall Inflammation and a Multilevel Cellular Immune Response in Humans. Arterioscler Thromb Vasc Biol. 2017; 37 (5): 969–975. DOI: 10.1161/ATVBAHA.116.308834.

[44] Paone S., Baxter A.A., Hulett M.D., Poon I.K.H. Endothelial cell apoptosis and the role of endothelial cell-derived extracellular vesicles in the progression of atherosclerosis. Cell Mol Life Sci. 2019; 76 (6): 1093–1106. DOI: 10.1007/s00018-018-2983-9.

[45] Gruzdeva O.V., Borodkina D.A., Akbasheva O.E. et al. Adipokino-cytokine profile of adipocytes of epicardial adipose tissue in coronary heart disease on the background of visceral obesity. Obesity and metabolism 2017; 14 (4): 38–45. DOI: 10.14341 / OMET2017438-45

[46] Yang X.J., Liu F., Feng N. et al. Berberine Attenuates Cholesterol Accumulation in Macrophage Foam Cells by Suppressing AP-1 Activity and Activation of the Nrf2/HO-1 Pathway. J Cardiovasc Pharmacol. 2020; 75 (1): 45–53. DOI: 10.1097/FJC.0000000000000769.

[47] Upadhye A, Sturek J.M., McNamara C.A. 2019 Russell Ross Memorial Lecture in Vascular Biology: B Lymphocyte-Mediated Protective Immunity in Atherosclerosis. Arterioscler Thromb Vasc Biol. 2020; 40 (2): 309–322. DOI: 10.1161/ATVBAHA.119.313064.

[48] Bilyutin-Aslanyan S.R., Khaitsev N.V., Balashov L.D., Kravtsova A.A. The role of dyslipidemia and inflammatory proteins in the development of isolated and multifocal atherosclerotic damage to the vessels of the brain and heart. Russian biomedical research 2017; 2 (4): 26–32 (in Russian).

[49] Билютин-Асланян С.Р., Хайцев Н.В., Балашов Л.Д., Кравцова А.А. Роль дислипидемии и воспалительных белков в развитии изолированного и мультифокального атеросклеротического повреждения сосудов головного мозга и сердца. Российские биомедицинские исследования 2017; 2 (4): 26–32.

[50] Kotova Yu.A., Zuykova A.A., Strakhova N.V., Krasnorutskaya O.N. Development of an information panel for laboratory diagnosis of myocardial infarction risk in patients with stable coronary heart disease. Medical alphabet. 2019; 1 (9): 33–37 (in Russian).

[51] Котова Ю.А., Зуйкова А.А., Страхова Н.В., Красноруцкая О.Н. Разработка информационной панели для лабораторной диагностики риска инфаркта миокарда у пациентов со стабильной ишемической болезнью сердца. Медицинский алфавит 2019; 1 (9): 33–37.

[52] Labudovic D., Kostovska I., Tosheska Trajkovska K. et al. Lipoprotein (a) – Link between Atherogenesis and Thrombosis. Prague Med Rep. 2019; 120 (2–3): 39–51. DOI: 10.14712/23362936.2019.9.

[53] Alessenko A.V., Zateyshchikov D.A., Lebedev A.Т., Kurochkin I.N. Participation of Sphingolipids in the Pathogenesis of Atherosclerosis. Kardiologiia 2019; 59 (8): 77–87. DOI: 10.18087/cardio.2019.8.10270.

[54] Zalova T.B. The role of lipoprotein-associated phospholipase A2 in the development of vascular remodeling and atherosclerosis of the main arteries. Bulletin of KRSU 2016; 16 (7): 89–91 (in Russian).

[55] Залова Т.Б. Роль липопротеин-ассоциированной фосфолипазы А2 в развитии сосудистого ремоделирования и атеросклероза магистральных артерий. Вестник КРСУ 2016; 16 (7): 89–91.

[56] Solovieva L.N. Laboratory tests and a biopsychosocial approach for examining patients with atherosclerosis of brachiocephalic arteries. Regional blood circulation and microcirculation 2017; 16–2 (62): 4–16 (in Russian).

[57] Соловьева Л.Н. Лабораторные тесты и биопсихосоциальный подход при обследовании пациентов с атеросклерозом брахиоцефальных артерий. Региональное кровообращение и микроциркуляция 2017; 16-2 (62): 4–16.

[58] Metelskaya V.A. Atherosclerosis: multi-marker diagnostic panels. Russian Journal of Cardiology 2018; 23 (8): 65–72. DOI: 10.15829/1560-4071-2018-8-65-72 (in Russian)

[59] Метельская В.А. Атеросклероз: мультимаркерные диагностические панели. Российский кардиологический журнал 2018; 23 (8): 65–72. DOI: 10.15829/1560-4071-2018-8-65-72

[60] Magruk M.A., Mosikyan A.A., Babenko A.Yu. Biomarkers associated with atherogenesis: current status and promising directions. Russian Journal of Cardiology 2019; 24 (12): 148–152. DOI: 10.15829 / 1560-4071-2019-12-148-152 (in Russian)

[61] Магрук М.А., Мосикян А.А., Бабенко А.Ю. Биомаркеры, ассоциированные с атерогенезом: актуальный статус и перспективные направления. Российский кардиологический журнал 2019; 24 (12): 148–152. DOI: 10.15829/1560-4071-2019-12-148-152

[62] Tabaei S., Tabaee S.S. DNA methylation abnormalities in atherosclerosis. Artif Cells Nanomed Biotechnol. 2019; 47 (1): 2031–2041. DOI: 10.1080/21691401.2019.1617724.

[63] Tabaei S., Tabaee S.S. DNA methylation abnormalities in atherosclerosis. Artif Cells Nanomed Biotechnol 2019; 47 (1): 2031–2041. DOI: 10.1080/21691401.2019.1617724.

[64] Schatz U., Fischer S., Müller G. et al. Cardiovascular risk factors in patients with premature cardiovascular events attending the University of Dresden Lipid Clinic. Atheroscler Suppl. 2019; 40: 94–99. DOI: 10.1016/j.atherosclerosissup.2019.08.044.

[65] Varvel S., McConnell J.P., Tsimikas S. Prevalence of Elevated Lp (a) Mass Levels and Patient Thresholds in 532 359 Patients in the United States. Arterioscler Thromb Vasc Biol. 2016; 36 (11): 2239–2245.

[66] Zueva I.B., Baratashvili G.G., Krivonosov D.S. et al. Lipoprotein (a) as a factor of cardiovascular risk. The current state of the problem. Bulletin of the Russian Military Medical Academy 2017; 1 (57): 219–225 (in Russian).

[67] Зуева И.Б., Бараташвили Г.Г., Кривоносов Д.С. и др. Липопротеин (а) как фактор сердечно-сосудистого риска. Современное состояние проблемы. Вестник Российской военно-медицинской академии 2017; 1 (57): 219–225.

[68] Titov V.N., Schekotova A.P. Oleic, palmitic triglycerides, very low density lipoproteins. Atherosclerosis, atherosclerosis of the arteries and the pathogenesis of coronary heart disease. Perm Medical Journal 2019; 36 (1): 102–117. DOI: 10.17816/pmj361102-117 (in Russian)

[69] Титов В.Н., Щекотова А.П. Олеиновые, пальмитиновые триглицериды, липопротеины очень низкой плотности. Атеросклероз, атероматоз артерий и патогенез ишемической болезни сердца. Пермский медицинский журнал 2019; 36 (1): 102–117. DOI: 10.17816/pmj361102-117

[70] Titov V.N., Sazhina N.N., Evteeva N.M. Ozone oxidizes oleic fatty acid with the highest reaction rate constant, while palmitic acid does not oxidize at all. The development of physicochemical parameters of substrates and the role in phylogenesis. Clinical laboratory diagnostics 2019; 64 (3): 132–139 (in Russian).

[71] Титов В.Н., Сажина Н.Н., Евтеева Н.М. Озон окисляет олеиновую жирную кислоту с наиболее высокой константой скорости реакции, пальмитиновую же не окисляет вообще. Развитие физико-химических параметров субстратов и роль в филогенезе. Клиническая лабораторная диагностика 2019; 64 (3): 132–139.

[72] Vrablík M. Current and future trends in the treatment of dyslipidemias. Vnitr Lek. 2019; 65 (10): 643–650.

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