Nascent high density lipoproteins formed by ABCA1 resemble lipid rafts and are structurally organized by three apoA-I monomers

Sorci‐Thomas, Mary G.; Owen, John S.; Fulp, Brian; Bhat, Sujata V.; Zhu, Xuewei; Parks, John S.; Shah, Dharika; Jerome, W. Gray; Gerelus, Mark; Zabalawi, Manal; Thomas, Michael J.

doi:10.1194/jlr.m026674

Cited by 108 publications

(159 citation statements)

References 98 publications

Supporting

Mentioning

147

Contrasting

Order By: Relevance

“…Whereas the adventitial lymphatic vessels are now accepted as important modulators of cholesterol transport between the atherosclerotic lesion and the bloodstream, the apoA‐I (apolipoprotein A‐I) has been identified as a key regulator of cellular cholesterol efflux via the ABCA1 receptor present at the cell surface 29, 30. ApoA‐I is the main protein constituent of plasma high‐density lipoprotein (HDL) and participates in its highly heterogeneous properties 31, 32.…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein A‐I Modulates Atherosclerosis Through Lymphatic Vessel‐Dependent Mechanisms in Mice

Milasan

Jean

Dallaire

et al. 2017

JAHA

View full text Add to dashboard Cite

BackgroundSubcutaneously injected lipid‐free apoA‐I (apolipoprotein A‐I) reduces accumulation of lipid and immune cells within the aortic root of hypercholesterolemic mice without increasing high‐density lipoprotein–cholesterol concentrations. Lymphatic vessels are now recognized as prerequisite players in the modulation of cholesterol removal from the artery wall in experimental conditions of plaque regression, and particular attention has been brought to the role of the collecting lymphatic vessels in early atherosclerosis‐related lymphatic dysfunction. In the present study, we address whether and how preservation of collecting lymphatic function contributes to the protective effect of apoA‐I.Methods and ResultsAtherosclerotic Ldlr −/− mice treated with low‐dose lipid‐free apoA‐I showed enhanced lymphatic transport and abrogated collecting lymphatic vessel permeability in atherosclerotic Ldlr −/− mice when compared with albumin‐control mice. Treatment of human lymphatic endothelial cells with apoA‐I increased the adhesion of human platelets on lymphatic endothelial cells, in a bridge‐like manner, a mechanism that could strengthen endothelial cell–cell junctions and limit atherosclerosis‐associated collecting lymphatic vessel dysfunction. Experiments performed with blood platelets isolated from apoA‐I‐treated Ldlr −/− mice revealed that apoA‐I decreased ex vivo platelet aggregation. This suggests that in vivo apoA‐I treatment limits platelet thrombotic potential in blood while maintaining the platelet activity needed to sustain adequate lymphatic function.ConclusionsAltogether, we bring forward a new pleiotropic role for apoA‐I in lymphatic function and unveil new potential therapeutic targets for the prevention and treatment of atherosclerosis.

show abstract

Section: Introductionmentioning

confidence: 99%

Apolipoprotein A‐I Modulates Atherosclerosis Through Lymphatic Vessel‐Dependent Mechanisms in Mice

Milasan

Jean

Dallaire

et al. 2017

JAHA

View full text Add to dashboard Cite

show abstract

“…All helixto-helix interactions present in the double belt between two molecules of apoA-I in a disc ( Fig. 6C ) ( [112][113][114][115][116]. There are variations in the distributions of classes of PL molecules across the HDL species, and larger particles are relatively FC-enriched.…”

Section: Apoa-i Organization In Spherical Hdlmentioning

confidence: 99%

New insights into the determination of HDL structure by apolipoproteins

Phillips

2013

Journal of Lipid Research

150

106

View full text Add to dashboard Cite

This article is available online at http://www.jlr.orgThe purpose of this review is to summarize current understanding of how apolipoproteins (apoA-I in particular) determine the structures of HDL particles. The focus is on recent advances in the fi eld, so the coverage of the literature on HDL structure is not comprehensive. Knowledge of HDL structure at the molecular level is critical for understanding how this lipoprotein achieves the multiple functions elaborated in other reviews in this thematic series.In human plasma, HDL is a heterogeneous collection of particles ranging 7-12 nm in diameter and 1.063-1.21 g/ml in density ( 1-4 ). The predominant species of HDL are spherical microemulsion particles, in which a core of neutral cholesteryl ester (CE) and triacylglycerol (TG) is encapsulated by a monolayer of phospholipid (PL), unesterifi ed (free) cholesterol (FC), and protein ( 5 ). The protein and PL constituents comprise approximately 50 and 25%, respectively, of the mass of such particles, with the CE, FC, and TG components making up the remainder. Larger, less dense HDL particles have a higher lipidto-protein mass ratio. Approximately 70% of total plasma HDL protein is apoA-I (which is present in normolipidemic human plasma at ‫ف‬ 130 mg/dl), and it is located in essentially every HDL particle. The second most abundant protein is apoA-II, which comprises 15-20% of total plasma HDL protein, but this component is not present in all HDL particles. In human plasma, about 25% of apoA-I is present in HDL particles containing only apoA-I (LpA-I); the remaining HDL particles contain both apoA-I and apoA-II (LpA-I+A-II), typically in a molar ratio of 1-2/1 ( 6 ). ApoA-I and apoA-II are the "scaffold" proteins that primarily determine HDL particle structure. Other members of the exchangeable apolipoprotein gene family that are Abstract Apolipoprotein (apo)A-I is the principal protein component of HDL, and because of its conformational adaptability, it can stabilize all HDL subclasses. The amphipathic ␣ -helix is the structural motif that enables apoA-I to achieve this functionality. In the lipid-free state, the helical segments unfold and refold in seconds and are located in the N-terminal two thirds of the molecule where they are loosely packed as a dynamic, four-helix bundle. The C-terminal third of the protein forms an intrinsically disordered domain that mediates initial binding to phospholipid surfaces, which occurs with coupled ␣ -helix formation. The lipid affi nity of apoA-I confers detergent-like properties; it can solubilize vesicular phospholipids to create discoidal HDL particles with diameters of approximately 10 nm. Such particles contain a segment of phospholipid bilayer and are stabilized by two apoA-I molecules that are arranged in an anti-parallel, double-belt conformation around the edge of the disc, shielding the hydrophobic phospholipid acyl chains from exposure to water. The apoA-I molecules are in a highly dynamic state, and they stabilize discoidal particles of different sizes by certain s...

show abstract

“…Depending on the detergents employed, ABCA1 has been reported to reside either in detergent-soluble membrane or partly in DRM; ABCA1 was recovered in detergent-soluble membrane when TX100 was used ( 35 ), while a fraction of this protein was recovered in DRM prepared using Lubrol WX ( 36 ). A recent work showed that lipid composition of nascent HDL particles generated by the ABCA1/apoA-I system is similar to that of lipid rafts ( 53 ). Heterogeneity of lipid raft domains has been reported; the protein and lipid contents/ compositions of DRM vary greatly depending on the detergents used ( 44,54 ).…”

Section: Abca1 Is Present In the Cholesterol-rich Membrane Domainmentioning

confidence: 99%

ABCA1-dependent sterol release: sterol molecule specificity and potential membrane domain for HDL biogenesis

Yamauchi

Yokoyama

Chang

2016

Journal of Lipid Research

View full text Add to dashboard Cite

Nascent high density lipoproteins formed by ABCA1 resemble lipid rafts and are structurally organized by three apoA-I monomers

Cited by 108 publications

References 98 publications

Apolipoprotein A‐I Modulates Atherosclerosis Through Lymphatic Vessel‐Dependent Mechanisms in Mice

Apolipoprotein A‐I Modulates Atherosclerosis Through Lymphatic Vessel‐Dependent Mechanisms in Mice

New insights into the determination of HDL structure by apolipoproteins

ABCA1-dependent sterol release: sterol molecule specificity and potential membrane domain for HDL biogenesis

Contact Info

Product

Resources

About