Autologous low-density lipoprotein labelling allows characterization of human atherosclerotic lesions in vivo as to presence of foam cells and endothelial coverage

1991 ◽  
Vol 18 (12) ◽  
Author(s):  
Irene Virgolini ◽  
F. Rauscha ◽  
Graziana Lupattelli ◽  
P. Angelberger ◽  
A. Ventura ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Foam Cells ◽  
Low Density ◽  
Atherosclerotic Lesions

Abstract 288: Atheroprotective Effect of Probucol Is Related to Its Heme Oxygenase 1 Activation and Subsequent Suppression of Oxidized Low-Density Lipoprotein--Induced Dendritic Cell Maturation

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Aijun Sun ◽  
Xueting Jin ◽  
Jingjing Zhao ◽  
Keqiang Wang ◽  
Fang Xu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Heme Oxygenase ◽  
High Fat Diet ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
High Fat ◽  
Atherosclerotic Lesions

Aims: Probucol, an agent characterized by lipid-lowering and anti-oxidant property, retards atherosclerosis effectively. Our study aimed to test the hypothesis that probucol might act its anti-athersclerotic role by suppressing maturation of human monocyte-derived dendritic cells (h-monDC). Furthermore, we also used a LDLR-/- mice model fed a high-fat diet to detect whether probucol also perform its anti-atherosclerotic effect on suppressing DCs maturation in vivo. Methods: H-monDCs were derived by incubating purified human monocytes with GM-CSF and IL-4. H-monDCs were pre-incubated with or without probucol and stimulated by oxidized low-density lipoprotein (ox-LDL) in the presence or absence of heme oxygenase (HO-1) siRNA. In vivo studies, streptozotocin (STZ) induced LDLR-/- mice were fed either a high-fat (HF) diet or added with 0.5% probucol for 4 months. Expression of h-monDC membrane molecules and mice splenic CD11c+DC membrane molecules were analyzed by FACS, cytokines were measured by ELISA and the STAT1/CIITA associated signaling pathway was determined by Western blotting. Mice aortic lesions were observed by En face staining and the expression of CD11c+DCs within atherosclerotic plaques were shown under confocal microscopy. Results: Ox-LDL promoted h-monDC maturation and TNF-a production; and up-regulated STAT1 701 phosphorylation by activating HO-1 in STAT1/CIITA signaling pathway. These effects were inhibited by probucol. Knocking down HO-1 with specific siRNA blocked these effects of probucol. In LDLR-/- mice fed a high-fat diet, probucol treatment significantly regressed aortic atherosclerotic lesions, suppressed splenic CD11c+DCs maturation and IL-12p70 production; and resulted in absence of CD11c+DCs within atherosclerotic lesions. Conclusions: Our study indicated that probucol effectively suppressed maturation of h-monDC induced by ox-LDL through HO-1 activation, and retarded atherosclerosis at least partly through inhibiting maturations of CD11c+DCs in LDLR-/- mice.

scholarly journals Characterization of binding sites for acetylated low density lipoprotein in the rat liver in vivo and in vitro.

1985 ◽  
Vol 4 (5) ◽  
pp. 1157-1162 ◽  
Author(s):  
H.A. Dresel ◽  
E. Friedrich ◽  
D.P. Via ◽  
G. Schettler ◽  
H. Sinn
Keyword(s):  
Rat Liver ◽  
Binding Sites ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density

Abstract 3625: Targeted Ultra-Small Iron Oxide Particles for In Vivo MR Detection of Atherosclerotic Lesions Using Antibodies against Oxidized Low Density Lipoprotein

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Karen Briley-Saebo ◽  
Peter X Shaw ◽  
Claudia Calcagno ◽  
Seung-Hyuk Choi ◽  
Valentin Fuster ◽  
...  
Keyword(s):  
Iron Oxide ◽  
Vulnerable Plaque ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Foam Cells ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Iron Oxide Particles ◽  
Oxide Particles

Background: Oxidized low-density lipoprotein (OxLDL) plays a key role in the progression and destabilization of atherosclerotic plaque. Preliminary studies indicate that gadolinium (Gd) micelles labeled with oxidation-specific antibodies allow for specific targeting of vulnerable plaque. Due to issues associated with Gd toxicity (caused by retention and bio-transformation of the micelles), clinical translation of this platform may be limited. Iron oxides are recognized as safe and effective contrast agents for MRI. As a result, it was hypothesized that lipid coated ultra-small iron oxide particles (LUSPIOs) containing murine antibodies that bind malondialde-hyde lysine (MDA2) or oxidized phospholipids (EO6) associated with oxLDL may allow for the development of a safe platform for in vivo detection of vulnerable plaque. Materials and Results: Untargeted, MDA2, and EO6 labeled LUSPIOs were prepared and characterized with respect to efficacy, pharmacokinetics, and biodistribution in Apolipoprotein deficient mice (ApoE−/−). MRI was performed at 9.4T prior to and 24 hrs after LUSPIO administration (4 mg Fe/kg) using both gradient echo and positive contrast GRASP sequences. MDA2 and EO6 increased the particle size, blood half-life, and MR efficacy of the LUSPIOs, relative to untargeted particles. Only limited signal attenuation was observed following administration of untargeted LUSPIO. MRI and microscopy revealed that MDA2 and EO6 LUSPIOs accumulate within oxLDL rich foam cells (Fig.1 ). Conclusions: This study suggests that biocompatible LUSPIOs may provide a clinically translatable platform for the MR detection of oxLDL rich foam cells in humans. This research has received full or partial funding support from the American Heart Association, AHA National Center.

Abstract 1454: Targeted Molecular Imaging Probes For In Vivo MR Detection Of Atherosclerotic Lesions Using Antibodies Against Oxidized Low Density Lipoprotein

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Karen C Briley-Saebo ◽  
Willem Mulder ◽  
Peter X Shaw ◽  
Seung-Hyuk Choi ◽  
Venkatesh Mani ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Mr Imaging ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Atherosclerotic Lesions ◽  
Molecular Imaging Probes ◽  
Imaging Probes

Background: Oxidized low-density lipoprotein (OxLDL) plays a key role in the initiation, progression and destabilization of atherosclerotic plaque. Molecular imaging probes that target OxLDL may allow in vivo detection of vulnerable plaques. In this study, magnetic resonance imaging (MRI) was used to detect atherosclerotic lesions in apolipoprotein deficient mice (ApoE−/−) using micelles comprised of gadolinium lipids, fluorescent rhodamine, PEG-lipids, and MDA2, a murine monoclonal antibody that binds malondialdehyde (MDA) lysine epitopes present in OxLDL. Materials and Results: Untargeted micelles, MDA2-labeled micelles and nonspecific polyclonal IgG micelles were prepared and characterized with respect to OxLDL binding capacity, pharmacokinetics, and biodistribution in wild type (WT) and ApoE−/− mice. MR imaging was performed at 9.4T over a 3-week interval after administration of 0.075 mmol Gd/kg micelles. MDA2 increased the micelle size, blood half-life, and MR efficacy relative to untargeted and IgG-micelles. Maximal plaque enhancement (>125%) was observed 72 hours post MDA2-micelle injection (Figure ). Untargeted and IgG-micelles did not exhibit significant wall enhancement at any of the time points studied. Confocal microscopy revealed that MDA2-micelles accumulate within foam cells associated with atherosclerotic plaque. WT mice showed no significant MR wall enhancement for any of the micelles studied. Conclusions: MR imaging using MDA2-micelles demonstrates specific targeting of OxLDL and foam cells and provides excellent MR image quality. This study suggests that it may be feasible to image similar atherosclerotic lesions in humans with MRI.

Oxidation of Plasma Low-Density Lipoprotein Accelerates Its Accumulation and Degradation in the Arterial Wall In Vivo

Circulation ◽  
1996 ◽  
Vol 94 (7) ◽  
pp. 1698-1704 ◽  
Author(s):  
Klaus Juul ◽  
Lars B. Nielsen ◽  
Klaus Munkholm ◽  
Steen Stender ◽  
Børge G. Nordestgaard
Keyword(s):  
Arterial Wall ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density

scholarly journals Interaction of 4-hydroxynonenal-modified low-density lipoproteins with the fibroblast apolipoprotein B/E receptor

1986 ◽  
Vol 234 (1) ◽  
pp. 245-248 ◽  
Author(s):  
W Jessup ◽  
G Jurgens ◽  
J Lang ◽  
H Esterbauer ◽  
R T Dean
Keyword(s):  
Apolipoprotein B ◽  
Negative Charge ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipid Peroxidation Product ◽  
Modified Low Density Lipoproteins ◽  
Peroxidation Product

The incorporation of the lipid peroxidation product 4-hydroxynonenal into low-density lipoprotein (LDL) increases the negative charge of the particle, and decreases its affinity for the fibroblast LDL receptor. It is suggested that this modification may occur in vivo, and might promote atherogenesis.

scholarly journals Biochemical and cytotoxic characteristics of an in vivo circulating oxidized low density lipoprotein (LDL-).

1994 ◽  
Vol 35 (4) ◽  
pp. 669-677
Author(s):  
H.N. Hodis ◽  
D.M. Kramsch ◽  
P. Avogaro ◽  
G. Bittolo-Bon ◽  
G. Cazzolato ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein
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