Oxidized low‐density lipoprotein‐induced expression of ABCA1 in blood monocytes precedes coronary atherosclerosis and is associated with plaque complexity in hypercholesterolemic pigs

Geeraert, Benjamine; Keyzer, Dieuwke De; Davey, Penelope C.; Crombé, Florence; Benhabilès, Nora; Holvoet, Paul

doi:10.1111/j.1538-7836.2007.02786.x

Cited by 30 publications

(30 citation statements)

References 31 publications

(43 reference statements)

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“…In such cases, lesion composition is similar to that of early-stage human atherosclerosis (Casani et al, 2005). Plasma lipid common markers in pigs after a high-fat/highcholesterol diet have been reported by many authors (Dixon et al, 1999;Geeraert et al, 2007). However, only two papers determined the mRNA levels of PPARα, SREBP1 and some of their target genes in liver and extra-hepatic tissues of pigs subjected to different fat-enriched diets in absence of cholesterol (Duran-Montgé et al, 2009a and2009b).…”

Section: Introductionmentioning

confidence: 99%

“…There are few reports on the modulation of lipid homeostasis by diet in pigs despite the fact that pigs and minipigs are widely used as animal models for important human pathologies such as atherosclerosis. A hypercholesterolemic diet is a validated model for inducing experimental atherosclerosis (Dixon et al, 1999;Geeraert et al, 2007;Chatzizisis et al, 2008). Pigs can develop hypercholesterolemia and atherosclerotic lesions after the administration of high-cholesterol diets, reaching plasma cholesterol levels similar to those in humans.…”

Section: Introductionmentioning

confidence: 99%

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Modulation of lipid homeostasis in response to continuous or intermittent high-fat diet in pigs

Puccinelli

Gervasi

Trivella

et al. 2015

Animal

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A high-fat diet is known to induce atherosclerosis in animal models. Dietary factors and timing of atherogenic food delivery may affect plasma lipoprotein content composition and its potential atherogenic effect. Increasingly often, humans spend periods/days eating in a completely unregulated way, ingesting excessive amounts of food rich in oils and fats, alternating with periods/days when food intake is more or less correct. We investigate the effect on lipid homeostasis of a high-fat diet administered either continuously or intermittently. We investigated control pigs receiving standard diet (C, n = 7), pigs receiving a high-fat diet every day for 10 weeks (CHF, n = 5), and pigs receiving a high-fat diet every other week for 10 weeks (IHF, n = 7). IHF animals were shown to have a different lipid profile compared with CHF animals, with a significant increase in high-density lipoproteins (HDL) levels with respect to C and CHF groups. CHF also showed significantly higher values of TC/HDL cholesterol compared with C and IHF. Hepatic expression analysis of genes involved in lipid homeostasis showed an increasing trend of nuclear receptor LXRα along with its target genes in the CHF group and in the IHF group, whereas SREBP2 and LDLr were significantly inhibited. A significant correlation was found between ABCA1 expression and circulating levels of HDL-C. Periodic withdrawals of a high-fat atherogenic diet compared with a regular administration results in a different adaptive response of lipoprotein metabolism, which leads to a significantly higher plasma level of HDL-C and lower TC/HDL-C.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Modulation of lipid homeostasis in response to continuous or intermittent high-fat diet in pigs

Puccinelli

Gervasi

Trivella

et al. 2015

Animal

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“…These lipid-loaded macrophages, termed foam cells, are characteristic of a reversible early cellular phase of atherosclerotic lesions. Progressive lipid accumulation leads to further escalation of inflammatory responses and infiltration of inflammatory cells (26). Through this process, early cellular lesions are transformed to late, fibrous, atherosclerotic plaques.…”

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confidence: 99%

25-Hydroxycholesterol-3-sulfate attenuates inflammatory response via PPARγ signaling in human THP-1 macrophages

Shen²,

Ma³

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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The nuclear receptor peroxisome proliferator-activated receptors (PPARs) are important in regulating lipid metabolism and inflammatory responses in macrophages. Activation of PPAR␥ represses key inflammatory response gene expressions. Recently, we identified a new cholesterol metabolite, 25-hydroxycholesterol-3-sulfate (25HC3S), as a potent regulatory molecule of lipid metabolism. In this paper, we report the effect of 25HC3S and its precursor 25-hydroxycholesterol (25HC) on PPAR␥ activity and on inflammatory responses. Addition of 25HC3S to human macrophages markedly increased nuclear PPAR␥ and cytosol IB and decreased nuclear NF-B protein levels. PPAR␥ response element reporter gene assays showed that 25HC3S significantly increased luciferase activities. PPAR␥ competitor assay showed that the Ki for 25HC3S was ϳ1 M, similar to those of other known natural ligands. NF-B-dependent promoter reporter gene assays showed that 25HC3S suppressed TNF␣-induced luciferase activities only when cotransfected with pcDNAI-PPAR␥ plasmid. In addition, 25HC3S decreased LPSinduced expression and release of IL-1␤. In the PPAR␥-specific siRNA transfected macrophages or in the presence of PPAR␥-specific antagonist, 25HC3S failed to increase IB and to suppress TNF␣ and IL-1␤ expression. In contrast to 25HC3S, its precursor 25HC, a known liver X receptor ligand, decreased nuclear PPAR␥ and cytosol IB and increased nuclear NF-B protein levels. We conclude that 25HC3S acts in macrophages as a PPAR␥ ligand and suppresses inflammatory responses via the PPAR␥/IB/NF-B signaling pathway.peroxisome proliferator-activated receptor-␥; oxysterols; oxysterol sulfation; cholesterol metabolites; inflammatory response; macrophages; nuclear factor-B signaling pathway MACROPHAGES ARE THE KEY CELLULAR PLAYERS in the pathogenesis of atherosclerosis. In the early stage of atherosclerosis, macrophages in arterial walls accumulate lipids. These lipid-loaded macrophages, termed foam cells, are characteristic of a reversible early cellular phase of atherosclerotic lesions. Progressive lipid accumulation leads to further escalation of inflammatory responses and infiltration of inflammatory cells (26). Through this process, early cellular lesions are transformed to late, fibrous, atherosclerotic plaques. Physiological or pharmacological maneuvers that reduce macrophage lipids and inflammatory responses may be effective in preventing or reversing atherosclerosis.Nuclear receptors are ligand-activated transcription factors that regulate the expression of target genes to affect processes as diverse as reproduction, inflammation, development, and metabolism (17). Nuclear receptor peroxisome proliferatoractivated receptors (PPARs) play major roles in the regulation of lipid metabolism, glucose homeostasis, and inflammatory processes and may be ideal targets for therapeutic management strategies for cardiovascular diseases (4,6,11,16,23,42). PPAR␥ appears particularly important in regulating genes involved in lipid metabolism and inflammation (1,8,20,21). The PPAR␥...

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“…Decreased ABCA1 protein levels in tissue of carotid plaques collected from the patients with advanced atherosclerosis confirms previous findings (25) for ABCA1 protein expression based on semiquantitative Western blot analysis. There is evidence that the extensive lipid accumulation in advanced atherosclerotic plaques despite of inducing ABCA1 transcription is associated with impaired lipid efflux from foam cells most likely due to reduced levels of ABCA1 protein (reviewed in 37) and/or reduced activity (38,39). In advanced atherosclerotic lesions, macrophages accumulate large amounts of free cholesterol (40), which leads to the degradation of ABCA1 protein in these macrophages (41).…”

Section: Abca1 Protein Elisa For Human Tissues and Cells 2265mentioning

confidence: 99%

A novel enzyme immunoassay specific for ABCA1 protein quantification in human tissues and cells

Paul

Meyer

Leidl

et al. 2008

Journal of Lipid Research

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ATP-binding cassette transporter A1 (ABCA1) mediates the transport of cholesterol and phospholipids from cells to lipid-poor HDL and maintains cellular lipid homeostasis. Impaired ABCA1 function plays a role in lipid disorders, cardiovascular disease, atherosclerosis, and metabolic disorders. Despite the clinical importance of ABCA1, no method is available for quantifying ABCA1 protein. We developed a sensitive indirect competitive ELISA for measuring ABCA1 protein in human tissues using a commercial ABCA1 peptide and a polyclonal anti-ABCA1 antibody. The ELISA has a detection limit of 8 ng/well (0.08 mg/l) with a working range of 9-1000 ng/well (0.09-10 mg/l). Intra-and interassay coefficient of variations (CVs) were 6.4% and 9.6%, respectively. Good linearity (r 5 0.97-0.99) was recorded in serial dilutions of human arterial and placental crude membrane preparations, and fibroblast lysates. The ELISA measurements for ABCA1 quantification in reference arterial tissues corresponded well with immunoblot analysis. The assay performance and clinical utility was evaluated with arterial tissues obtained from 15 controls and 44 patients with atherosclerotic plaques. ABCA1 protein concentrations in tissue lysates were significantly lower in patients (n 5 24) as compared with controls (n 5 5; 9.37 6 0.82 vs. 17.03 6 4.25 mg/g tissue; P , 0.01). The novel ELISA enables the quantification of ABCA1 protein in human tissues and confirms previous semiquantitative immunoblot results.-Paul, V., H. H. D. Meyer, K. Leidl, S. Soumian, and C. Albrecht. A novel enzyme immunoassay specific for ABCA1 protein quantification in human tissues and cells.

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Oxidized low‐density lipoprotein‐induced expression of ABCA1 in blood monocytes precedes coronary atherosclerosis and is associated with plaque complexity in hypercholesterolemic pigs

Cited by 30 publications

References 31 publications

Modulation of lipid homeostasis in response to continuous or intermittent high-fat diet in pigs

Modulation of lipid homeostasis in response to continuous or intermittent high-fat diet in pigs

25-Hydroxycholesterol-3-sulfate attenuates inflammatory response via PPARγ signaling in human THP-1 macrophages

A novel enzyme immunoassay specific for ABCA1 protein quantification in human tissues and cells

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