Lipid composition of circulating multiple-modified low density lipoprotein

Zakiev, Emile; Sukhorukov, Vasily N.; Melnichenko, Alexandra А.; Sobenin, Igor A.; Ivanova, Ekaterina A.; Orekhov, Alexander N.

doi:10.1186/s12944-016-0308-2

Cited by 39 publications

(38 citation statements)

References 16 publications

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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: 89%

“…Such separation is possible by using a column with RCA 120 immobilized on CNBractivated agarose. [12,21] Compared with sialylated LDL, desialylated LDL particles are smaller in size and contain more oxysterols, and less phospholipids and antioxidants. [12] In terms of the ability to induce intracellular deposition of lipids, the desialylated LDL fraction is atherogenic.…”

Section: Discussionmentioning

confidence: 99%

“…[12,21] Compared with sialylated LDL, desialylated LDL particles are smaller in size and contain more oxysterols, and less phospholipids and antioxidants. [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.…”

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%

“…[10,11] It was hence accepted that LDL is required to undergo structural alterations or chemical modifications to become atherogenic. [12] However, modified LDL particles are still not considered as clinical biomarkers or therapeutic targets because of insufficient evidence. Therefore, additional studies, both basic and clinical, are necessary to fill the existing gap in the knowledge.…”

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: 89%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

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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Targeting the Microenvironment of Vulnerable Atherosclerotic Plaques: An Emerging Diagnosis and Therapy Strategy for Atherosclerosis

et al. 2022

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Atherosclerosis is considered one of the primary causes of cardiovascular diseases (CVDs). Unpredictable rupture of the vulnerable atherosclerotic plaques triggers adverse cardiovascular events such as acute myocardial syndrome and even sudden cardiac death. Therefore, assessing the vulnerability of atherosclerotic plaques and early intervention are of significance in reducing CVD mortality. Nanomedicine possesses tremendous advantages in achieving the integration of the diagnosis and therapy of atherosclerotic plaques because of its magnetic, optical, thermal, and catalytic properties. Based on the pathological characteristics of vulnerable plaques, stimuli‐responsive nanoplatforms and surface‐functionalized nanoagents are designed and have drawn great attention for accomplishing the precise imaging and treatment of vulnerable atherosclerotic plaques due to their superior properties, such as high bioavailability, lesion‐targeting specificity, on‐demand cargo release, and low off‐target damage. Here, the characteristics of vulnerable plaques are generalized, and some targeted strategies for boosting the accuracy of plaque vulnerability evaluation by imaging and the efficacy of plaque stabilization therapy (including antioxidant therapy, macrophage depletion therapy, regulation of lipid metabolism therapy, anti‐inflammation therapy, etc.) are systematically summarized. In addition, existing challenges and prospects in this field are discussed, and it is believed to provide new thinking for the diagnosis and treatment of CVDs in the near future.

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Lipid‐based gene delivery to macrophage mitochondria for atherosclerosis therapy

Zakirov

Zhang

Grechko

et al. 2020

Pharmacology Res & Perspec

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Atherosclerosis with associated cardiovascular diseases remains one of the main causes of disability and death worldwide, requiring development of new solutions for prevention and treatment. Macrophages are the key effectors of a series of events involved in atherogenesis, such as inflammation, plaque formation, and changes in lipid metabolism. Some of these events were shown to be associated with mitochondrial dysfunction and excessive mitochondrial DNA (mtDNA) damage. Moreover, macrophages represent a promising target for novel therapeutic approaches that are based on the expression of various receptors and nanoparticle uptake. Lipid‐based gene delivery to mitochondria is considered to be an interesting strategy for mtDNA damage correction. To date, several nanocarriers and their modifications have been developed that demonstrate high transfection efficiency and low cytotoxicity. This review discusses the possibilities of lipid‐based gene delivery to macrophage mitochondria for atherosclerosis therapy.

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Lipid composition of circulating multiple-modified low density lipoprotein

Cited by 39 publications

References 16 publications

Small dense and desialylated low density lipoprotein in diabetic patients

Small dense and desialylated low density lipoprotein in diabetic patients

Targeting the Microenvironment of Vulnerable Atherosclerotic Plaques: An Emerging Diagnosis and Therapy Strategy for Atherosclerosis

Lipid‐based gene delivery to macrophage mitochondria for atherosclerosis therapy

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