Regulation of the concentration of pre.beta. high-density lipoprotein in normal plasma by cell membranes and lecithin-cholesterol acyltransferase activity

Miida, Takashi; Kawano, Motoharu; Fielding, C J; Fielding, Phoebe E.

doi:10.1021/bi00160a022

Cited by 107 publications

(79 citation statements)

References 28 publications

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“…However, this effect, which was associated with conversion of pre␤HDL to other HDL particles, is not observed if incubation is performed in the presence of fibroblasts, vascular smooth muscle cells, or macrophages. 23 In Figure 1, it was demonstrated that incubation of plasma with macrophages for various lengths of time (up to 6 hours) does not change its ability to promote subsequent cholesterol efflux from the foam cells during a 30 minutes incubation. This result allowed us to design experiments in which the effect of mast cell granule remnants on the cholesterol efflux-inducing capacity of plasma could be studied for prolonged periods in a system comprising plasma, granule remnants, and macrophages.…”

Section: Effect Of Granule Remnants On 3 H-cholesterol Efflux Promotementioning

confidence: 95%

“…20,21 They can also be formed when apoA1 is incubated with macrophages, 22 fibroblasts, or vascular smooth muscle cells. 23 These pre␤LpA1 particles are discoidal and remove cholesterol from cells very rapidly by a process that involves interaction with protease-sensitive domains on the cell surface. 24,25 From pre␤ 1 LpA1, cell-derived cholesterol is rapidly transferred to the bulk of ␣-LpA1, presumably by conversion of particles of the former type into those of the latter.…”

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confidence: 99%

“…However, when plasma was incubated with cells of various types, such as fibroblasts or HL-60 macrophages, this decrease was inhibited. 23 Compared with other HDL species, the apoA1 in pre␤ 1 LpA1 has been shown to expose different epitopes to monoclonal antibodies, 28 -30 indicating a different conformation and, hence, suggesting differences in its accessibility to modification by proteolysis, oxidation, or glycation.…”

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confidence: 99%

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Depletion of Preβ ₁ LpA1 and LpA4 Particles by Mast Cell Chymase Reduces Cholesterol Efflux From Macrophage Foam Cells Induced by Plasma

Lee

Eckardstein

Lindstedt

et al. 1999

ATVB

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Abstract-Exposure of the LpA1-containing particles present in HDL 3 and plasma to a minimal degree of proteolysis by the neutral protease chymase from exocytosed rat mast cell granules (granule remnants) leads to a reduction in the high-affinity component of cholesterol efflux from macrophage foam cells. In this study, we demonstrate for the first time, a role for mast cell chymase in the depletion of the lipid-poor minor components of HDL that are specifically involved in reverse cholesterol transport as initial acceptors of cellular cholesterol. Thus, addition of proteolytically active granule remnants or human skin chymase to cholesterol-loaded macrophages of mouse or human origin incubated with human apoA1, ie, a system in which pre␤ 1 LpA1 is generated, resulted in a sharp reduction in the high-affinity cholesterol efflux promoted by apoA1. As determined by nondenaturing 2-dimensional polyacrylamide gradient gel electrophoresis, the granule remnants effectively depleted the pre␤ 1 LpA1, but not the ␣LpA1, in HDL 3 and in plasma during incubation at 37°C for Ͻ1 hour. Incubation of plasma with granule remnants for 1 hour also led to near disappearance of the LpA4 -1 and LpA4 -2 particles, but did not affect the distribution of the apoA2-containing lipoproteins present in the plasma. We conclude that the reduced ability of granule remnant-treated HDL 3 and granule remnant-treated plasma to induce cholesterol efflux from macrophage foam cells is caused by selective depletion by mast cell chymase of quantitatively minor A1-and A4-containing subpopulations of HDL. Because these particles, ie, pre␤ 1 LpA1 and LpA4, are efficient acceptors of cholesterol from cell surfaces, their depletion by mast cells may block the initiation of reverse cholesterol transport in vivo and thereby favor foam cell formation in the arterial intima, the site of atherogenesis.

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Section: Effect Of Granule Remnants On 3 H-cholesterol Efflux Promotementioning

confidence: 95%

mentioning

confidence: 99%

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confidence: 99%

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Depletion of Preβ ₁ LpA1 and LpA4 Particles by Mast Cell Chymase Reduces Cholesterol Efflux From Macrophage Foam Cells Induced by Plasma

Lee

Eckardstein

Lindstedt

et al. 1999

ATVB

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“…Cellular UC acquired by pre-β-HDL eventually appears on the more abundant, α-migrating HDL species, with the concurrent loss of pre-β-HDL species. [4][5][6]10 It is unclear whether this movement of cellular cholesterol from pre-β-HDL species to α-HDL is due solely to transformation (remodeling) of the pre-β particles into α-HDL or if a transfer of cholesterol (shuttling) also occurs. Definitive studies aimed at tracking the flow of UC have been difficult, owing to the low abundance of pre-β particles, which represent <4% of the cholesterol mass in plasma, and to the rapid transformation into α-HDL by the action of lecithinxholesterol acyltransferase in whole serum.…”

Section: Author Manuscriptmentioning

confidence: 99%

Remodeling and Shuttling

Rodrigueza

Williams

Rothblat

et al. 1997

ATVB

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In normal physiology, cells are exposed to cholesterol acceptors of different sizes simultaneously. The current study examined the possible interactions between two different classes of acceptors, one large (large unilamellar phospholipid vesicles, LUVs) and one small (HDL or other small acceptors), added separately or in combination to Fu5AH rat hepatoma cells. During a 24-hour incubation, LUVs of palmitoyl-oleoyl phosphatidylcholine at 1 mg phospholipid (PL) per milliliter extracted ≈20% of cellular unesterified cholesterol (UC) label and mass in a slow, continuous fashion (half-time [t½] for UC efflux was ≈50 hours) and human HDL 3 at 25 μg PL per milliliter extracted ≈15% cellular UC label with no change in cellular cholesterol mass (t½ of ≈8 hours). In contrast, the combination of LUVs and HDL 3 extracted over 90% of UC label (t½ of ≈4 hours) and ≈50% of the UC mass, indicating synergy. To explain this synergy, specific particle interactions were examined, namely, remodeling, in which the two acceptors alter each other's composition and thus the ability to mobilize cellular cholesterol, and shuttling, in which the small acceptor ferries cholesterol from cells to the large acceptor. To examine remodeling, LUVs and HDL were coincubated and reisolated before application to cells. This HDL became UC depleted, PL enriched, and lost a small amount of apolipoprotein A-I. Compared with equivalent numbers of control HDL particles, remodeled HDL caused faster efflux (t½ ≈4 hours) and exhibited a greater capacity to sequester cellular cholesterol over 24 hours (≈38% versus ≈15% for control HDL), consistent with their enrichment in PL. Remodeled LUVs still extracted ≈20% of cellular UC. Thus, remodeling accounted for some but not all of the synergy between LUVs and HDL. To examine shuttling, several approaches were used. First, reisolation of particles after an 8-hour exposure to cells revealed that HDL contained very little of the cellular UC label. The label was found almost entirely with the LUVs, suggesting that LUVs continuously stripped the HDL of cellular UC. Second, bidirectional flux studies demonstrated that LUVs blocked the influx of HDL UC label into cells, while the rate of efflux of cellular UC was maintained. These kinetic effects explained the massive net loss of cellular UC to LUVs with HDL. Third, cyclodextrin, an artificial small acceptor that does not acquire PL and hence does not become remodeled, exhibitedCorrespondence to Dr Michael C. Phillips, Department of Biochemistry, Medical College of Pennsylvania and Hahnemann University, 2900 Queen Ln, Philadelphia, PA 19129. Portions of this work were published in abstract form in Abstracts Submitted to the Council on Arteriosclerosis for the 68th Scientific Sesssions of the American Heart Association. 1995:54. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript substantial synergy with LUVs, supporting shuttling. Thus, the presence of large and small acceptors together can overcome intrinsic deficiencies in...

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“…In one pathway, called the specific pathway, pre 1-HDL interacts with cell membranes and takes up cholesterol via ATP-binding cassette (ABC) A1 expressed on the cell surface. Pre 1-HDL conversion to -HDL is one of the critical steps in this specific RCT and is mediated by lecithin: cholesterol acyltransferase (LCAT) 8) …”

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confidence: 99%

Pitavastatin Decreases Plasma Pre.BETA.1-HDL Concentration and Might Promote its Disappearance Rate in Hypercholesterolemic Patients

Kawano

Nagasaka

Yagyu

et al. 2008

JAT

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Aim: Pre 1-HDL is involved in the initial step of cholesterol efflux from peripheral cells and plays an important role in reverse cholesterol transport. We studied the effect of pitavastatin on the HDL subfraction profile, pre 1-HDL concentration and its disappearance rate. Methods: Twenty-nine hypercholesterolemic patients were treated with pitavastatin at 2 mg/day for 4 weeks, and plasma levels of total cholesterol (TC), triglyceride, HDL-cholesterol (C), HDL2-C, HDL3-C, pre 1-HDL, LCAT activity, and CETP mass were assayed. The pre 1-HDL disappearance rate was determined as the difference in pre 1-HDL concentration before and after incubation at 37 for 90 min divided by the pre-incubation pre 1-HDL concentration. Results: Pitavastatin led to significant decreases in TC by 26.9% and LDL-C by 39.8%. HDL-C and HDL2-C increased significantly by 6.0% and 9.0%, respectively, but there was no significant change in HDL3-C. Pre 1-HDL concentration significantly decreased ( 8.7%; p 0.05); however, its disappearance rate significantly increased (13.0%; p 0.05). There were significant decreases in both LCAT activity and CETP mass. Conclusion: Although pitavastatin decreased plasma pre 1-HDL concentration, it increased the pre 1-HDL disappearance rate. These data suggest that pitavastatin might promote the early step of reverse cholesterol transport. J Atheroscler

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Regulation of the concentration of pre.beta. high-density lipoprotein in normal plasma by cell membranes and lecithin-cholesterol acyltransferase activity

Cited by 107 publications

References 28 publications

Depletion of Preβ ₁ LpA1 and LpA4 Particles by Mast Cell Chymase Reduces Cholesterol Efflux From Macrophage Foam Cells Induced by Plasma

Depletion of Preβ ₁ LpA1 and LpA4 Particles by Mast Cell Chymase Reduces Cholesterol Efflux From Macrophage Foam Cells Induced by Plasma

Remodeling and Shuttling

Pitavastatin Decreases Plasma Pre.BETA.1-HDL Concentration and Might Promote its Disappearance Rate in Hypercholesterolemic Patients

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Regulation of the concentration of pre.beta. high-density lipoprotein in normal plasma by cell membranes and lecithin-cholesterol acyltransferase activity

Cited by 107 publications

References 28 publications

Depletion of Preβ 1 LpA1 and LpA4 Particles by Mast Cell Chymase Reduces Cholesterol Efflux From Macrophage Foam Cells Induced by Plasma

Depletion of Preβ 1 LpA1 and LpA4 Particles by Mast Cell Chymase Reduces Cholesterol Efflux From Macrophage Foam Cells Induced by Plasma

Remodeling and Shuttling

Pitavastatin Decreases Plasma Pre.BETA.1-HDL Concentration and Might Promote its Disappearance Rate in Hypercholesterolemic Patients

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Product

Resources

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Depletion of Preβ ₁ LpA1 and LpA4 Particles by Mast Cell Chymase Reduces Cholesterol Efflux From Macrophage Foam Cells Induced by Plasma

Depletion of Preβ ₁ LpA1 and LpA4 Particles by Mast Cell Chymase Reduces Cholesterol Efflux From Macrophage Foam Cells Induced by Plasma