scholarly journals The Dynamics of Oxidized LDL during Atherogenesis

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Hiroyuki Itabe ◽  
Takashi Obama ◽  
Rina Kato
Keyword(s):  
Time Course ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Oxidized Low Density Lipoprotein ◽  
Atherosclerotic Lesions ◽  
Long Duration ◽  
Course Changes ◽  
Classical Hypothesis

Accumulating evidence indicates that oxidized low-density lipoprotein (OxLDL) is a useful marker for cardiovascular disease. The uptake of OxLDL by scavenger receptors leads to the accumulation of cholesterol within the foam cells of atherosclerotic lesions. OxLDL has many stimulatory effects on vascular cells, and the presence of OxLDL in circulating blood has been established. According to the classical hypothesis, OxLDL accumulates in the atherosclerotic lesions over a long duration, leading to advanced lesions. However, recent studies on time-course changes of OxLDLin vivoraised a possibility that OxLDL can be transferred between the lesions and the circulation. In this paper, thein vivodynamics of OxLDL are discussed.

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 Polar phospholipids from bovine endogenously oxidized low density lipoprotein interfere with follicular thecal function

2005 ◽  
Vol 35 (3) ◽  
pp. 531-545 ◽  
Author(s):  
B Löhrke ◽  
T Viergutz ◽  
B Krüger
Keyword(s):  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Ldl Oxidation ◽  
Low Density ◽  
Oxidized Low Density Lipoprotein ◽  
Steroidogenic Enzymes ◽  
Cox 2

The role of endogenously oxidized low density lipoprotein (oxLDL) in follicular steroidogenic regulation is unknown. Information may be important in order to elucidate ovulatory dysregulation in disordered lipid metabolism. To obtain specific data, we studied the effect of polar phospholipids (PL) isolated from oxLDL with different endogenous levels of lipohydroperoxides (LHP) on the thecal expression of mRNA encoding steroidogenic enzymes and cyclooxygenase 2 (COX-2), and on the thecal production of superoxide and progesterone. Large (preovulatory) bovine follicles were used and analyses of thecal fragments from single follicles were performed by radioimmunoassays, chemiluminescence assays and quantitative RT-PCR. Basal concentration of mRNA for several lipoprotein receptors exceeded by about 10-times the basal level of mRNA encoding steroidogenic enzymes, suggesting that preovulatory theca receptors may favour uptake of oxLDL. PL (5–11 pmol phosphorus/ml) decreased (up to 0.5-times the control) progesterone synthesis, production of superoxide and levels of P450 cholesterol side chain cleavage (P450 scc), 3β-hydroxysteroid dehydrogenase and COX-2 mRNA. Abundance of COX-2 transcripts in thecal tissue incubated with forskolin depended on the progesterone/17β-oestradiol ratio of the follicle fluid, i.e. the previous microenvironment in vivo. PL effects were mimicked by the platelet-activating factor (PAF). WEB 2086, a PAF receptor blocker, did not always abolish these responses, suggesting that the effects were not mediated solely by this receptor. PAF interfered dose-dependently with LH-induced responses, indicating interference with LH signalling. PL from mildly oxidized LDL (0.5 nmol/ml LHP) tended to exert greater effects than PL from oxLDL containing 1.5 nmol/ml LHP. In consideration of the known physiologic role of progesterone, COX-2 and possibly superoxide, these results provide evidence for a potential of PL from oxLDL to induce ovulatory dysregulation and suggest that the extent of the LDL oxidation seems to be important for interfering with thecal responses to the preovulatory LH surge.

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.

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

scholarly journals The neurorepellent, Slit2, prevents macrophage lipid loading by inhibiting CD36-dependent binding and internalization of oxidized low-density lipoprotein

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bushra Yusuf ◽  
Ilya Mukovozov ◽  
Sajedabanu Patel ◽  
Yi-Wei Huang ◽  
Guang Ying Liu ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Super Resolution ◽  
Low Density ◽  
Dependent Manner ◽  
Oxidized Low Density Lipoprotein ◽  
Cortical Actin ◽  
Cytoskeletal Remodeling ◽  
Atherosclerotic Lesions ◽  
Modified Lipoproteins

AbstractAtherosclerosis is characterized by retention of modified lipoproteins, especially oxidized low density lipoprotein (oxLDL) within the sub-endothelial space of affected blood vessels. Recruited monocyte-derived and tissue-resident macrophages subsequently ingest oxLDL by binding and internalizing oxLDL via scavenger receptors, particularly CD36. The secreted neurorepellent, Slit2, acting through its transmembrane receptor, Roundabout-1 (Robo-1), was previously shown to inhibit recruitment of monocytes into nascent atherosclerotic lesions. The effects of Slit2 on oxLDL uptake by macrophages have not been explored. We report here that Slit2 inhibits uptake of oxLDL by human and murine macrophages, and the resulting formation of foam cells, in a Rac1-dependent and CD36-dependent manner. Exposure of macrophages to Slit2 prevented binding of oxLDL to the surface of cells. Using super-resolution microscopy, we observed that exposure of macrophages to Slit2 induced profound cytoskeletal remodeling with formation of a thick ring of cortical actin within which clusters of CD36 could not aggregate, thereby attenuating binding of oxLDL to the surface of cells. By inhibiting recruitment of monocytes into early atherosclerotic lesions, and the subsequent binding and internalization of oxLDL by macrophages, Slit2 could represent a potent new tool to combat individual steps that collectively result in progression of atherosclerosis.

Oxidative stress augments pulmonary hypertension in chronically hypoxic mice overexpressing the oxidized LDL receptor

2013 ◽  
Vol 305 (2) ◽  
pp. H155-H162 ◽  
Author(s):  
Sayoko Ogura ◽  
Tatsuo Shimosawa ◽  
ShengYu Mu ◽  
Takashi Sonobe ◽  
Fumiko Kawakami-Mori ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Vascular Remodeling ◽  
Chronic Hypoxia ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Ros Generation ◽  
Low Density ◽  
Ros Production ◽  
Oxidized Low Density Lipoprotein

Chronic hypoxia is one of the main causes of pulmonary hypertension (PH) associated with ROS production. Lectin-like oxidized low-density lipoprotein receptor (LOX)-1 is known to be an endothelial receptor of oxidized low-density lipoprotein, which is assumed to play a role in the initiation of ROS generation. We investigated the role of LOX-1 and ROS generation in PH and vascular remodeling in LOX-1 transgenic (TG) mice. We maintained 8- to 10-wk-old male LOX-1 TG mice and wild-type (WT) mice in normoxia (room air) or hypoxia (10% O2 chambers) for 3 wk. Right ventricular (RV) systolic pressure (RVSP) was comparable between the two groups under normoxic conditions; however, chronic hypoxia significantly increased RVSP and RV hypertrophy in LOX-1 TG mice compared with WT mice. Medial wall thickness of the pulmonary arteries was significantly greater in LOX-1 TG mice than in WT mice. Furthermore, hypoxia enhanced ROS production and nitrotyrosine expression in LOX-1 TG mice, supporting the observed pathological changes. Administration of the NADPH oxidase inhibitor apocynin caused a significant reduction in PH and vascular remodeling in LOX-1 TG mice. Our results suggest that LOX-1-ROS generation induces the development and progression of PH.

scholarly journals Oxidized LDL but not angiotensin II induces the interaction between LOX-1 and AT1 receptors

2020 ◽  
Author(s):  
Li Lin ◽  
Ning Zhou ◽  
Le Kang ◽  
Qi Wang ◽  
Jian Wu ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Direct Interaction ◽  
Cardiomyocyte Hypertrophy ◽  
Oxidized Low Density Lipoprotein ◽  
Protein Activation

Oxidized low-density lipoprotein (Ox-LDL) can induce cardiac hypertrophy, but the mechanism is still unclear. Here we elucidate the role of angiotensin II (AngII) receptor (AT1-R) in Ox-LDL-induced cardiomycyte hypertrophy. Inhibition of Ox-LDL receptor LOX-1 and AT1-R rather than AngII abolished Ox-LDL-induced hypertrophic responses. Similar results were obtained from the heart of mice lacking endogenous Ang II and their cardiomyocytes. Ox-LDL but not AngII induced binding of LOX-1 to AT1-R, and the inhibition of LOX-1 or AT1-R rather than AngII abolished the association of these two receptors. Ox-LDL-induced ERKs phosphorylation in LOX-1 and AT1-R-overexpression cells and the binding of both receptors were suppressed by the mutants of LOX-1 (Lys266Ala/Lys267Ala) or AT1-R (Glu257Ala), however, the AT1-R mutant lacking Gq protein-coupling ability only abolished the ERKs phosphorylation. The phosphorylation of ERKs induced by Ox-LDL in LOX-1 and AT1-R-overexpression cells was abrogated by Gq protein inhibitor but not by Jak2, Rac1 and RhoA inhibitors. Therefore, the direct interaction between LOX-1 and AT1-R and the downstream Gq protein activation are important mechanisms for Ox-LDL- but not AngII-induced cardiomyocyte hypertrophy

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