High-Density Lipoprotein Infusions

Takata, Kohei; Bartolo, Belinda A. Di; Nicholls, Stephen J.

doi:10.1016/j.ccl.2017.12.012

Cited by 3 publications

(3 citation statements)

References 56 publications

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“…17,18 However, in more recent investigations, infusion of sHDL did not show a convincing clinical benefit. 19 In the context of this therapeutic approach, a recombinant high-molecular mass variant of human apoA-I, named Tetranectin-apoA-I, has been engineered by fusing three apoA-I molecules with the trimerization domain of human tetranectin. 20 This trimeric apoA-I is not filtered by glomeruli and hence shows a prolonged half-life as compared to normal apoA-I, 20 thus potentially improving its efficacy.…”

Section: Introductionmentioning

confidence: 99%

Infusions of Large Synthetic HDL Containing Trimeric apoA-I Stabilize Atherosclerotic Plaques in Hypercholesterolemic Rabbits

Parolini

Adorni

Busnelli

et al. 2019

Canadian Journal of Cardiology

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Background: Among strategies to reduce the remaining risk of cardiovascular disease, interest has focused on using infusions of synthetic HDL (sHDL). Methods: New Zealand rabbits underwent a perivascular injury at both carotids and were randomly allocated into two protocols: 1) a single dose study, where rabbits were treated with a single infusion of sHDL containing a trimeric form of human apoA-I (TN-sHDL, 200 mg/kg) or with Placebo; 2) a multiple dose study, where four groups of rabbits were treated five times with Placebo or TN-sHDL at different doses (8, 40, 100 mg/kg). Plaque changes were analysed in vivo by IntraVascular UltraSound (IVUS). Blood was drawn from rabbits for biochemical analyses and cholesterol efflux capacity (CEC) evaluation. Results: In both protocols, atheroma volume in the Placebo groups increased between the first and the second IVUS evaluation. A stabilization or a slight regression was instead observed vs baseline in the TN-sHDL treated groups (p<0.005 vs Placebo post-infusion). TN-sHDL treatment caused a sharp rise of plasma free cholesterol levels and a significant increase of total CEC. Histological analysis of carotid plaques showed a reduced macrophage accumulation in TN-sHDL treated rabbits compared to Placebo (p<0.05). Conclusions: Our results demonstrate that acute and sub-acute treatments with TN-sHDL are effective in stabilizing atherosclerotic plaques in a rabbit model. This effect appears to be related to a reduced intra-plaque accumulation of inflammatory cells. Besides recent failures in proving its efficacy, sHDL treatment remains a fascinating therapeutic option for reduction of cardiovascular risk.

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Section: Introductionmentioning

confidence: 99%

Infusions of Large Synthetic HDL Containing Trimeric apoA-I Stabilize Atherosclerotic Plaques in Hypercholesterolemic Rabbits

Parolini

Adorni

Busnelli

et al. 2019

Canadian Journal of Cardiology

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“…HDL was formulated in clinical trials by combining serum-derived ApoAI with different phospholipid compositions, but the results were only moderately successful. One potential explanation is the heterogeneous nature of serum-derived ApoAI from HDL donors. ,− Indeed, HDL from CVD patients was less efficient in terms of cholesterol efflux, possibly reflecting the oxidation of the ApoAI protein and lipidome. ,, Interestingly, more recent clinical studies have indicated that the relationship between HDL concentration and CVD mortality is U-shaped rather than linear, suggesting that the quality of HDL is more important than the quantity for lowering LDL cholesterol. , …”

Section: Introductionmentioning

confidence: 99%

Multivalent Display of ApoAI Peptides on the Surface of Tobacco Mosaic Virus Nanotubes Improves Cholesterol Efflux

2022

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Atherosclerosis is a progressive cardiovascular disease in which cholesterol-rich plaques build up within arteries, increasing the risk of thrombosis, myocardial infarction, and stroke. One promising therapeutic approach is the use of high-density lipoprotein (HDL) biomimetic formulations based on ApoAI peptides that promote cholesterol efflux from plaques, ultimately leading to cholesterol excretion. Here, we describe the multivalent display of ApoAI peptides on the surface of protein nanotubes derived from the plant virus tobacco mosaic virus (TMV) and protein nanoparticles using virus-like particles from bacteriophage Qβ. Bioconjugation yielded ApoAI conjugates varying in size and morphology. We tested ABCA1-mediated cholesterol efflux using macrophage foam cells, the mitigation of reactive oxygen species in endothelial cells, and wound healing in endothelial cells. We found that the multivalent ApoAI platform, in particular the TMV-based nanotube, significantly improved the efficacy of cholesterol efflux compared to free peptides, Qβ nanoparticle formulations, and traditional HDL therapy. Finally, to better understand the mechanistic basis of enhanced cholesterol efflux, we used confocal microscopy to show that while native TMV was taken up by cells, TMV-ApoAI remained at the exterior of foam cell membranes and efflux was documented using fluorescent cholesterol. Together, these data highlight that high aspect ratio materials with multivalent display of ApoAI peptides offer unique capabilities promoting efficient cholesterol efflux and may find applications in cardiovascular therapy.

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“…Мутация апоА-I Milano впервые обнаружена в когорте итальянцев с низкой распространенностью атеросклероза, несмотря на очень низкий уровень ХС-ЛПВП (0,26-0,52 ммоль/л). Комплекс апоА-I Milano с фосфолипидом (1-пальмитоил-2-олеоил-sn-глицеро-3фосфохолин) известен как ETC-216 [53]. Внутривенное введение ETC-216 приводило к значительному снижению содержания липидов в атероматозной бляшке и вызывало быструю и значительную регрессию атеросклероза у кроликов и мышей [8].…”

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High-Density Lipoproteins: From Quantitative Measures to Functional Assessment and Therapy (Review of Literature)

Poteryaeva

Usynin

2023

RCLD

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The antiatherogenic role of high-density lipoproteins (HDL) is associated primarily with their participation in the reverse transport of excess cholesterol from peripheral tissues to the liver. The efficiency of this mechanism depends on the ability of apolipoprotein A-I (apoA-I), the main protein component of HDL, to capture cholesterol from cells. It is known that the acceptor properties of this protein can change under the influence of various factors. This review discusses modern approaches aimed both at increasing the plasma level of HDL and preserving their native functional properties. As one of the key criteria of HDL functionality it is proposed to determine the ability of HDL to accept labeled cholesterol from macrophages. Studies have shown that injection of recombinant HDL or apoA-I mimetic peptides accelerates cholesterol efflux from peripheral tissues, improves vascular endothelial state, and leads to regression of atherosclerotic plaque. Thus, therapy with recombinant HDL/apoA-I may become an effective way to treat cardiovascular diseases caused by cholesterol accumulation in the vascular wall.

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High-Density Lipoprotein Infusions

Cited by 3 publications

References 56 publications

Infusions of Large Synthetic HDL Containing Trimeric apoA-I Stabilize Atherosclerotic Plaques in Hypercholesterolemic Rabbits

Infusions of Large Synthetic HDL Containing Trimeric apoA-I Stabilize Atherosclerotic Plaques in Hypercholesterolemic Rabbits

Multivalent Display of ApoAI Peptides on the Surface of Tobacco Mosaic Virus Nanotubes Improves Cholesterol Efflux

High-Density Lipoproteins: From Quantitative Measures to Functional Assessment and Therapy (Review of Literature)

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