Toward reliable low-density lipoprotein ultrastructure prediction in clinical conditions: A small-angle X-ray scattering study on individuals with normal and high triglyceride serum levels

Jakubauskas, Dainius; Jansen, M.; Lyngsø, Jeppe; Cheng, Yumin; Pedersen, Jan Skov; Cárdenas, Marité

doi:10.1016/j.nano.2020.102318

Cited by 4 publications

(4 citation statements)

References 55 publications

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“…Recently, sdLDL fractions of normal and hyper triglyceridemic subjects were shown to have similar biochemical composition but different sizes and protein rich shell layer thicknesses [24] (Figure 2D). This suggests that LDL size and structure are not directly a consequence of composition and diet, mirroring the data found for individuals with a predisposition for sdLDL [45].…”

Section: Different Atherogenic Capacity Of Lipoprotein Subclassesmentioning

confidence: 90%

“…While both lipoprotein types are characterised by a lipid binding activity, their abilities to exchange lipids and to transport cholesterol differ drastically. Indeed, LDL mainly deposit lipids and cholesterol to artery walls, whereas the main role of HDL in the blood is to catalyse cholesterol efflux thereby removing excess cholesterol from macrophages [24].…”

Section: Lipoproteins and Atherosclerosismentioning

confidence: 99%

“…The detailed understanding of LDL ultrastructure seems necessary to evaluate the atherogenicity of the individual LDL subfractions with the ultimate aim to develop effective diagnostic and therapeutic tools against CVD. Indeed, the SAXS analysis of the total LDL fraction and its subfractions shows that SAXS has the potential to discern between LDL phenotypes directly from the total LDL measurement [24] ( Figure 2D), which could be used to extract information on the sdLDL structural parameters between subjects with a range of clinical conditions.…”

Section: Different Atherogenic Capacity Of Lipoprotein Subclassesmentioning

confidence: 99%

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Structure of Lipoproteins and Their Capacity for Lipid Exchange: Relevance for Development of Atherosclerosis and Its Treatment by HDL Therapy

Waldie¹,

Giudice²,

Cárdenas³

2021

Management of Dyslipidemia

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Atherosclerosis, the largest killer in the western world, arises from build-up of plaques at the artery walls and can result in cardiovascular disease. Low- and high-density lipoproteins are involved in the disease development by depositing and removing lipids to and from macrophages at the artery wall. These processes are complex and not fully understood. Thus, determining the specific roles of the different lipoprotein fractions involved is of fundamental importance for the treatment of the disease. In this chapter, we present the state of the art in lipoprotein structure with focus on the comparison between normolipidemic and hypertriglyceridemic individuals. Then we discuss lipid transfer between lipoproteins and receptor-free cellular membranes. Although these models lack any receptor, key clinical observations are mirrored by these, including increased ability of HDL to remove lipids, in contrast to the ability of LDL to deposit them. Also effects of saturated and unsaturated lipids in the presence and absence of cholesterol are revised. These models can then be used to understand the difference in functionality of lipoproteins from individuals showing different lipid profiles and have the potential to be used also for the development of new HDL therapies.

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Section: Different Atherogenic Capacity Of Lipoprotein Subclassesmentioning

confidence: 90%

Section: Lipoproteins and Atherosclerosismentioning

confidence: 99%

Section: Different Atherogenic Capacity Of Lipoprotein Subclassesmentioning

confidence: 99%

See 1 more Smart Citation

Structure of Lipoproteins and Their Capacity for Lipid Exchange: Relevance for Development of Atherosclerosis and Its Treatment by HDL Therapy

Waldie¹,

Giudice²,

Cárdenas³

2021

Management of Dyslipidemia

Self Cite

View full text Add to dashboard Cite

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“…In contrast to invasive imaging methods, non-invasive imaging techniques for atherosclerotic plaque detection with undoubted advantages, such as noninvasiveness, precision, high spatiotemporal resolution, and low toxicity, have taken a chief place [14,15]. So far, the main non-invasive imaging approaches for patients include ultrasound, X-ray, CT, and magnetic resonance imaging (MRI), having different uses [16][17][18]. Of interest, vascular calcification, a hallmark of atherosclerosis, can be detected by CT, and lipid-rich necrotic core and hemorrhage can be additionally captured by MRI with high sensitivity [19,20].…”

Section: Introductionmentioning

confidence: 99%

Engineering molecular nanoprobes to target early atherosclerosis: Precise diagnostic tools and promising therapeutic carriers

Zan¹,

An²,

Wu³

et al. 2023

Nanotheranostics

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Atherosclerosis, an inflammation-driven chronic blood vessel disease, is a major contributor to devastating cardiovascular events, bringing serious social and economic burdens. Currently, non-invasive diagnostic and therapeutic techniques in combination with novel nanosized materials as well as established molecular targets are under active investigation to develop integrated molecular imaging approaches, precisely visualizing and/or even effectively reversing early-stage plaques. Besides, mechanistic investigation in the past decades provides many potent candidates extensively involved in the initiation and progression of atherosclerosis. Recent hotly-studied imaging nanoprobes for detecting early plaques mainly including optical nanoprobes, photoacoustic nanoprobes, magnetic resonance nanoprobes, positron emission tomography nanoprobes, and other dual- and multi-modality imaging nanoprobes, have been proven to be surface functionalized with important molecular targets, which occupy tailored physical and biological properties for atherogenesis. Of note, these engineering nanoprobes provide long blood-pool residence and specific molecular targeting, which allows efficient recognition of early-stage atherosclerotic plaques and thereby function as a novel type of precise diagnostic tools as well as potential therapeutic carriers of anti-atherosclerosis drugs. There have been no available nanoprobes applied in the clinics so far, although many newly emerged nanoprobes, as exemplified by aggregation-induced emission nanoprobes and TiO 2 nanoprobes, have been tested for cell lines in vitro and atherogenic animal models in vivo , achieving good experimental effects. Therefore, there is an urgent call to translate these preclinical results for nanoprobes into clinical trials. For this reason, this review aims to give an overview of currently investigated nanoprobes in the context of atherosclerosis, summarize relevant published studies showing applications of different kinds of formulated nanoprobes in early detection and reverse of plaques, discuss recent advances and some limitations thereof, and provide some insights into the development of the new generation of more precise and efficient molecular nanoprobes, with a critical property of specifically targeting early atherosclerosis.

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miR‐125a‐3p aggravates ox‐LDL‐induced HUVEC injury through BAMBI

Xia

Zeng

2022

J Biochem & Molecular Tox

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Atherosclerosis (AS) is a chronic inflammatory disease characterized by the formation of atherosclerotic plaque in the intima of arteries. Among the known regulators of atherosclerosis, microRNAs (miRNAs) have been reported to play critical roles in lipoprotein homeostasis and plaque formation. But the roles of microRNA‐125a‐3p (miR‐125a‐3p) in the pathogenesis of AS remain unknown. Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low‐density lipoprotein (ox‐LDL) to construct the vascular injury model of AS pathogenesis in vitro. miR‐125a‐3p and BMP and activin membrane‐bound inhibitor (BAMBI) expression levels in HUVECs were then measured by quantitative real‐time polymerase chain reaction and western blot. The viability and apoptosis of HUVECs were analyzed by Cell Counting Kit‐8 assay, TUNEL assay, and flow cytometry, respectively. The relationship between BAMBI 3′‐untranslated region and miR‐125a‐3p was validated by dual luciferase reporter gene assay. miR‐125a‐3p expression was raised in HUVECs induced with ox‐LDL. In HUVECs, miR‐125a‐3p enhanced the effects of ox‐LDL treatment on repressing the viability and promoting the apoptosis of cells. Additionally, BAMBI was confirmed as a direct target of miR‐125a‐3p and BAMBI overexpression reversed the effects of miR‐125a‐3p on HUVECs. miR‐125a‐3p aggravates the dysfunction of HUVECs induced by ox‐LDL via BAMBI, which implies that miR‐125a‐3p is involved in the pathogenesis of AS.

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Toward reliable low-density lipoprotein ultrastructure prediction in clinical conditions: A small-angle X-ray scattering study on individuals with normal and high triglyceride serum levels

Cited by 4 publications

References 55 publications

Structure of Lipoproteins and Their Capacity for Lipid Exchange: Relevance for Development of Atherosclerosis and Its Treatment by HDL Therapy

Structure of Lipoproteins and Their Capacity for Lipid Exchange: Relevance for Development of Atherosclerosis and Its Treatment by HDL Therapy

Engineering molecular nanoprobes to target early atherosclerosis: Precise diagnostic tools and promising therapeutic carriers

miR‐125a‐3p aggravates ox‐LDL‐induced HUVEC injury through BAMBI

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