Deglycosylation of apo B-containing lipoproteins increase their ability to aggregate and to promote intracellular cholesterol accumulation<i>in vitro</i>

Aksenov, D. V.; Medvedeva, L.A.; Skalbe, T. A.; Sobenin, Igor A.; Tertov, V.V.; Gabbasov, Zufar; Popov, E. V.; Orekhov, Alexander N.

doi:10.1080/13813450802227915

Cited by 13 publications

(10 citation statements)

References 43 publications

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“…LDL(-) is associated with cardiovascular risks and myocardial infarction (90)(91)(92). LDL(-) particles are also prone to aggregation (12, 93), which promotes accumulation of intracellular cholesterol (94)(95)(96)(97). It was demonstrated that atherogenic modification of lipoprotein is responsible for its aggregation (97).…”

Section: Known Modified Ldl Types Present In Vivomentioning

confidence: 99%

Modified lipoproteins as biomarkers of atherosclerosis

Orekhov

Собенин

2018

Front Biosci

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Pathogenesis of atherosclerosis and the search for novel therapies and diagnostic markers remain major problems of modern medicine. Currently available therapeutic approaches are often not sufficiently effective, probably due to the complexity of the disease mechanisms. This review focuses on the evaluation of low density lipoprotein (LDL) and high density lipoprotein (HDL) as risk factors of atherosclerosis. We summarize the current paradigm of LDL involvement in atherogenesis and HDL presumably protective properties. We next discuss the available evidence for the protective effect of HDL and the consequences of HDL dysfunction. Finally, we question the currently widely accepted hypothesis of the central role of oxidized LDL in atherogenesis and present an alternative concept of multiple modification of LDL that confers its pro-atherogenic properties.

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Section: Known Modified Ldl Types Present In Vivomentioning

confidence: 99%

Modified lipoproteins as biomarkers of atherosclerosis

Orekhov

Собенин

2018

Front Biosci

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“…[12,13,23,32] We have found previously that LDL atherogenicity in CAD patients and diabetic patients correlates negatively with sialic acid levels. [13] Indeed, in vitro studies have shown that desialylated LDL treated with neuraminidase, which removes the sialic acid residues, results in a significant increase in LDL potency to induce lipid accumulation in cultured monocyte-macrophages or intimal cells.…”

Section: Discussionmentioning

confidence: 99%

“…[13] Indeed, in vitro studies have shown that desialylated LDL treated with neuraminidase, which removes the sialic acid residues, results in a significant increase in LDL potency to induce lipid accumulation in cultured monocyte-macrophages or intimal cells. [32] However, whether the loss of sialic acid in circulating LDL is the primary reason for their atherogenicity, remains unclear. The so-called desialylated LDL is characterized by several alterations to its chemical composition and physical properties, low sialic acid level being only one attribute of a wider scope of changes including the density, size, and electric charge of particles.…”

Section: Discussionmentioning

confidence: 99%

“…[12] In terms of the ability to induce intracellular deposition of lipids, the desialylated LDL fraction is atherogenic. [12,23,32] Several studies have reported an elevation of sialic acid serum levels in CHD patients, and also on its correlation with the severity of the coronary lesions. [33] Diabetic patients' LDL, by the first approach, appeared to have a decreased level of sialic acid, and further investigations have shown that this was due to an increased proportion of desialylated LDL fraction in patients' blood and a greater extent of its desialylation.…”

Section: Discussionmentioning

confidence: 99%

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Small dense and desialylated low density lipoprotein in diabetic patients

Sobenin¹,

Galitsyna²,

Grechko³

et al. 2017

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How to cite this article: Sobenin IA, Galitsyna EV, Grechko AV, Orekhov AN. Small dense and desialylated low density lipoprotein in diabetic patients. Vessel Plus 2017;1:29-37.Aim: This study was undertaken to investigate the physicochemical properties of modified low density lipoprotein (LDL) in diabetes. Methods: LDL from 10 type 1 and 10 type 2 diabetic patients, as well as LDL from 10 non-diabetic subjects, was subdivided into bound and nonbound fractions by affinity chromatography on Ricinus communis agglutinin-agarose, and further characterized by sialic acid content, hydrated density, electrophoretic mobility, and the ability to induce cholesterol deposition in cultured cells. Results: The non-bound LDL fraction was similar to native LDL from healthy subjects, with respect to its physicochemical properties, and did not produce intracellular cholesterol accumulation. The bound LDL fraction was characterized by several alterations differentiating it from non-bound LDL, namely, significantly lowered sialic acid content (by 35-50%, compared with non-bound LDL), increased electrophoretic mobility (by 40-50%), increased hydrated density (difference in modae, 5.6-5.9 mg/mL), and smaller particle size (difference in modae, 3.8-4.9 nm). Bound LDL possessed the ability to induce a 2.1-to 2.7-fold increase in intracellular cholesterol content. Conclusion: The results showed the presence of a dense, small, more electronegative, desialylated LDL subfraction in the blood of diabetic patients, which is in vivo modified atherogenic LDL.

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“…Агрегация ЛНП(-) была подробно исследована [42]. Как известно, объединение частиц ЛНП приводит к их атерогенности, то есть к способности ЛНП вызывать накопление внутриклеточного холестерина [43,44]. Неправильная укладка аполипопротеина является решающим фактором, ответственным за агрегацию ЛНП(-) [45].…”

Section: электроотрицательные лнпunclassified

Atherogenic modification of low-density lipoproteins

2016

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2 Российский экономический университет им. Г.В. Плеханова, 117997, Москва, Стремянный переулок, 36 3 НИИ атеросклероза (Сколково), а/я №21, 121609, Москва Одним из наиболее ранних проявлений атеросклероза является вне-и внутриклеточное отложение липидов, преимущественно эфиров холестерина, в артериальной интиме. В крови человека были обнаружены модифицированные липопротеины низкой плотности (ЛНП), которые, как предполагается, и вызывают накопление липидов в артериальной стенке, то есть являются атерогенными. В предлагаемом обзоре рассмотрены функциональные особенности и роль в атерогенезе важнейших разновидностей модифицированных ЛНП: окисленных ЛНП, мелких плотных ЛНП, электроотрицательных и, особенно, десиалированных ЛНП. Атерогенные ЛНП обладают многочисленными изменениями углеводного, белкового и липидного компонентов и могут быть названы множественно-модифицированными ЛНП. Множественные модификации ЛНП происходят в плазме человеческой крови и представляют собой каскад последовательных изменений в липопротеиновой частице: десиалирование, потеря липидов, уменьшение размера частиц, увеличение поверхностного электроотрицательного заряда и т.д. Авторы склонны считать и приводят доказательства того, что именно десиалирование является ключевым и первичным звеном этих изменений и дальнейшего развития патологии в клетках интимы. Помимо внутриклеточного накопления липидов, в работе представлены механизмы усиления потенциала атерогенности множественно-модифицированных ЛНП: влияние на пролиферацию клеток и фиброз, образование циркулирующих иммунных комплексов и агрегатов ЛНП.Ключевые слова: атерогенность, атеросклероз, десиалирование, внутриклеточное накопление липидов, липопротеины низкой плотности, окисление, транс-сиалидаза

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Deglycosylation of apo B-containing lipoproteins increase their ability to aggregate and to promote intracellular cholesterol accumulationin vitro

Cited by 13 publications

References 43 publications

Modified lipoproteins as biomarkers of atherosclerosis

Modified lipoproteins as biomarkers of atherosclerosis

Small dense and desialylated low density lipoprotein in diabetic patients

Atherogenic modification of low-density lipoproteins

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