<i>In vivo</i> kinetics of human apolipoprotein A‐I variants in rabbits

Saku,; Eckardstein, Von; Zhang, Bo; Liu, Ming; Jimi,; Ou,; Ohta,; Assmann,; Arakawa,

doi:10.1046/j.1365-2362.1999.00430.x

Cited by 8 publications

(5 citation statements)

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“…The AIM half-life of 40 hours evaluated in the present study is twice that of homologous rabbit or human apoA-I observed in kinetic studies performed in rabbits. 26,28 Similarly, kinetic studies of dimeric AIM in humans clearly indicated an increased residence time in the circulation compared with monomeric AIM or wild-type apoA-I. 29 This finding was recently confirmed in a clinical investigation comparing AIM to the chemically similar apoA-I Paris variant.…”

Section: Discussionmentioning

confidence: 87%

Recombinant Apolipoprotein A-I _Milano Infusion Into Rabbit Carotid Artery Rapidly Removes Lipid From Fatty Streaks

Chiesa

Monteggia

Marchesi

et al. 2002

Circulation Research

195

104

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Abstract-Apolipoprotein A-I Milano (AIM), a natural variant of human apolipoprotein A-I, confers to carriers a significant protection against vascular disease. In previous studies, administration of recombinant AIM-phospholipid (AIM-PL) complexes to hypercholesterolemic rabbits markedly inhibited neointimal formation after arterial injury; moreover, repeated injections of AIM-PL in apoE-deficient mice significantly reduced atherosclerosis progression. The objective of the present study was to determine if a single localized infusion of AIM-PL complexes administered directly to atheromatous lesions could promote plaque regression. Lipid-rich, atheromatous plaques were generated at both common carotid arteries of 25 rabbits by applying a perivascular electric injury, followed by 1.5% cholesterol diet for 90 days. Rabbits were infused with either saline, phospholipid vesicles, or 3 different AIM-PL doses (250, 500, or 1000 mg of protein) delivered through an intravascular ultrasound (IVUS) catheter positioned at the origin of the right carotid. The lesions at the left carotid artery were therefore exposed to the agents systemically. Infusion of AIM-PL at the 2 highest doses caused reduction of right carotid artery plaque area by the end a 90-minute infusion as assessed by IVUS analysis. Plaque area regression was confirmed by histology in carotid arteries receiving direct (500 and 1000 mg doses) and systemic (500 mg dose) delivery, 72 hours after the start of the treatment. Plaque lipid content was associated with significant and similar decreases in Oil Red O staining in both arteries. These results suggest AIM-PL complexes enhanced lipid removal from arteries is the mechanism responsible for the observed plaque changes.

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Section: Discussionmentioning

confidence: 87%

Recombinant Apolipoprotein A-I _Milano Infusion Into Rabbit Carotid Artery Rapidly Removes Lipid From Fatty Streaks

Chiesa

Monteggia

Marchesi

et al. 2002

Circulation Research

195

104

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“…Therefore, further investigation of their properties contributes to the beĴer understanding of their individual metabolism and physiological function (Davidson et al, 1995;Colvin & Parks, 1999). Such physiological role is a function of small size (Oram et al, 1981;Dory et al, 1986), high negative charge (Desrumaux et al, 1989;Dory et al, 1986;Sparks et al, 1995;Saku et al, 1999), high diffusion (Castro & Fielding, 1988), and low thermodynamic stability (Sparks et al, 1999) of the particles. The physico-chemical properties of macromolecules are commonly determined from the study of their displacement in solution by the effect of an external gradient of a potential caused by either electrical (electrophoresis) or gravitational (sedimentation) forces (Giddings, 1991).…”

Section: Discussionmentioning

confidence: 99%

Small high density lipoprotein subclasses: some of their physico-chemical properties and stability in solution.

Atmeh

Elrazeq²

2005

Acta Biochim Pol

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Small high density lipoproteins (SHDL) contribute to the protection from atherosclerosis, but detailed information about their properties is not available yet. We isolated four of the smallest HDL subclasses that contain apoA-I alone, the small lipoprotein A-I (SLpAI), by their separation on gradient polyacrylamide gel followed by electroelution. Their physico-chemical properties were calculated from their displacement in non-denaturing gradient polyacrylamide gel under the effect of electrical potential. The properties are: Stokes' radii 2.96-3.56 nm; molecular masses 42-70 kDa; net negative charge 7.2-13.5; surface charge densities 3139-4069 -esu.cm(-2); surface potentials 10.6-15.7 -mV; coefficients of friction 5.74-6.90 x 10(-8) g.s(-1); and diffusion coefficients 5.76-6.94 x 10(-7) cm(2).s(-1). We found that these particles were of low stability as they underwent molecular transformation into larger particles on storage. The estimated dimensions of these particles do not support ellipsoidal shape, therefore, the most probable shape is spherical; consequently, their hydrated characteristics were estimated. We conclude that these particles have high values of negative surface charge and diffusion coefficients, and are of low stability. Their small Stokes' radii were similar to each other and they are spherical and highly hydrated.

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“…Excess Na 125 I was removed by gel filtration using a PD-10 column (Amersham Pharmacia Biotech, Tokyo, Japan) and dialyzed against a solution of 0.85% NaCl. Human 125 I-apoA-I (specific activity: 2114 dpm/ng) was associated with unlabeled rabbit HDL overnight at 4°C and purified by ultracentrifugation before injection into the marginal auricular vein of Group 1 rabbits, as we described previously (25,38). Briefly, the mixture of human 125 I-apoA-I and rabbit HDL was adjusted to a density of 1.21 g/mL using solid KBr and ultracentrifuged using a TLA-100.3 rotor for 10 h at 541,000 × g and 4°C.…”

Section: Methodsmentioning

confidence: 99%

“…Human 125 I-apoA-I (specific activity: 604 dpm/ng) was associated with unlabeled rabbit HDL at 4°C overnight and purified by ultracentrifugation (25,38) before injection into the marginal auricular veins of Group 2 rabbits. Rabbit 125 I-apoA-I (specific activity: 613 dpm/ng) separated by the guanidine HCl method was reassociated with rabbit plasma for 30 min at 37°C, as described by Brousseau et al (39), and injected into Group 5 rabbits.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of apolipoprotein A‐I kinetics in rabbits in vivo using in situ and exogenous radioiodination methods

Zhang

Shimoji

Tanaka

et al. 2003

Lipids

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The kinetics of in vivo clearance of apolipoprotein (apo) A-I radioiodinated by the iodine monochloride (ICI) method of McFarlane [McFarlane, A.S. (1958) Efficient Trace-Labelling of Proteins with Iodine, Nature 182, 53] as modified by Bilheimer and co-workers [Bilheimer, D.W., Eisenberg, S., and Levy, R.I. (1972) The Metabolism of Very Low Density Lipoprotein Proteins. I. Preliminary in vitro and in vivo Observations, Biochim. Biophys. Acta 260, 212-221] and by using the IODO Beads Iodination Reagent were evaluated in rabbits. Both human apoA-I and rabbit HDL radioiodinated by the IODO Beads Iodination Reagent were cleared faster from plasma of rabbits than those radiolabeled by the ICI method. However, the different radiolabeling procedures in the ICI method, i.e., apoA-I radiolabeled either exogenously or in situ as a part of intact HDL, were not associated with a significant difference in the in vivo kinetics of apoA-I in rabbits if apoA-I was prepared by the guanidine HCI method and used fresh. 125I-ApoA-I subjected to delipidation and lyophilization was cleared only slightly faster from the plasma of rabbits than fresh 125I-apoA-I. We also found that apoA-I separated by the guanidine HCI method and used fresh was cleared faster from the plasma of rabbits when it was injected as free apoA-I without adding serum albumin or after in vitro incubation with rabbit HDL than when injected after reassociation with rabbit plasma. We conclude that the ICI method is a more appropriate radioiodination method for studying the in vivo kinetics of HDL than the IODO Beads Iodination Reagent and that the in vitro incubation conditions before injection are important factors that affect the in vivo kinetics of apo A-I.

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In vivo kinetics of human apolipoprotein A‐I variants in rabbits

Abstract: Genetic variants of apo A-I with a single amino acid substitution show abnormal kinetics, and the electric charge of a apo A-I variant could contribute to determining its kinetics in vivo in this xenologous model.

Cited by 8 publications

References 50 publications

Recombinant Apolipoprotein A-I _Milano Infusion Into Rabbit Carotid Artery Rapidly Removes Lipid From Fatty Streaks

Recombinant Apolipoprotein A-I _Milano Infusion Into Rabbit Carotid Artery Rapidly Removes Lipid From Fatty Streaks

Small high density lipoprotein subclasses: some of their physico-chemical properties and stability in solution.

Evaluation of apolipoprotein A‐I kinetics in rabbits in vivo using in situ and exogenous radioiodination methods

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In vivo kinetics of human apolipoprotein A‐I variants in rabbits

Abstract: Genetic variants of apo A-I with a single amino acid substitution show abnormal kinetics, and the electric charge of a apo A-I variant could contribute to determining its kinetics in vivo in this xenologous model.

Cited by 8 publications

References 50 publications

Recombinant Apolipoprotein A-I Milano Infusion Into Rabbit Carotid Artery Rapidly Removes Lipid From Fatty Streaks

Recombinant Apolipoprotein A-I Milano Infusion Into Rabbit Carotid Artery Rapidly Removes Lipid From Fatty Streaks

Small high density lipoprotein subclasses: some of their physico-chemical properties and stability in solution.

Evaluation of apolipoprotein A‐I kinetics in rabbits in vivo using in situ and exogenous radioiodination methods

Contact Info

Product

Resources

About

Recombinant Apolipoprotein A-I _Milano Infusion Into Rabbit Carotid Artery Rapidly Removes Lipid From Fatty Streaks

Recombinant Apolipoprotein A-I _Milano Infusion Into Rabbit Carotid Artery Rapidly Removes Lipid From Fatty Streaks