Modified low density lipoprotein from diabetic patients causes cholesterol accumulation in human intimal aortic cells

Sobenin, Igor A.; Tertov, V.V.; Koschinsky, T.; Bünting, C.; Slavina, E.S.; Dedov, Ivan I.; Orekhov, Alexander N.

doi:10.1016/0021-9150(93)90066-4

Cited by 76 publications

(46 citation statements)

References 34 publications

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“…[13] LDL particles carry a variety of modifications, which are usually inherently atherogenic, unlike native LDL. [10] The increase of a fraction of modified LDL can cause disruption of lipid metabolism and contribute to the development of atherosclerotic and metabolic diseases such as diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…[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. [13,14] This LDL fraction was also characterized by increased non-enzymatic glycation and altered lipid composition, namely, decreased content of esterified cholesterol and elevated level of lyso-phospholipids. [13,14] Taken together, these findings indicate that this LDL fraction with multiple modifications has marked atherogenic potency.…”

Section: Discussionmentioning

confidence: 99%

“…[13,14] This LDL fraction was also characterized by increased non-enzymatic glycation and altered lipid composition, namely, decreased content of esterified cholesterol and elevated level of lyso-phospholipids. [13,14] Taken together, these findings indicate that this LDL fraction with multiple modifications has marked atherogenic potency. In the present study, desialylated LDL from diabetic patients was additionally examined by density, particle size, and electrophoretic mobility to obtain a more complete physicochemical characterization of this atherogenic LDL fraction.…”

Section: Discussionmentioning

confidence: 99%

“…[13] LDL from diabetic patients was subdivided into two fractions by lectin chromatography on Ricinus communis agarose, wherein bound (desialylated) LDL showed substantial dissimilarity with non-bound (native) LDL with respect to chemical composition and atherogenic properties, i.e. it was just a fraction of in vivo modified LDL presumably responsible for lipid accumulation in cultured cells.…”

Section: Introductionmentioning

confidence: 99%

“…it was just a fraction of in vivo modified LDL presumably responsible for lipid accumulation in cultured cells. [13,14] In the past few years, it was demonstrated that even in healthy individuals, LDL is heterogeneous in size and hydrated density, and the presence of small dense LDL (sdLDL) in blood is associated with a higher risk of clinical manifestations of atherosclerosis. [15][16][17] We have shown that multiple-modified atherogenic LDL occurring in blood of atherosclerotic patients is characterized also by increased hydrated density, and therefore may be easily regarded as sdLDL.…”

Section: Introductionmentioning

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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

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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Phospholipids of Plasma Lipoproteins, Red Blood Cells and Atheroma, Analysis of

Ravandi

Kuksis

2000

Encyclopedia of Analytical Chemistry

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The large number of lipid classes and great complexity of molecular species present in blood plasma, red cells, platelets and atheromatous lesions requires a combination of analytical techniques for comprehensive analyses, including chemical and enzymatic derivatization of samples. In many instances only partial analyses are required, which can be accomplished by specific analytical techniques. This chapter describes the full spectrum of the methodology ranging from the most basic thin‐layer chromatography (TLC) to the detailed mass spectrometric assays. Traditional sample extraction by liquid–liquid partition is time‐consuming and involves large volumes of solvents. Liquid–solid extraction using adsorbent cartridges is more economical. At the present time total lipid extracts can be effectively assayed for lipid class content and molecular species composition by flow injection tandem mass spectrometry (MS/MS), while a more detailed analysis of complex lipid mixtures is provided by a combination of liquid chromatography with on‐line electrospray mass spectrometry (LC/ESMS). The new techniques permit completion of the analyses in a few hours, where previously several days or weeks may have been required. The soft ionization mass spectrometric techniques have permitted the recognition and detailed analysis of such minor components of blood as the lipid oxidation and glycation products often observed in disease.

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