Serum Opacity Factor Enhances HDL‐Mediated Cholesterol Efflux, Esterification and Anti Inflammatory Effects

Tchoua, Urbain; Rosales, Corina; Tang, Dongdong; Gillard, Baiba K.; Vaughan, Ashley M.; Lin, Hu Yu; Courtney, Harry S.; Pownall, Henry J.

doi:10.1007/s11745-010-3484-2

Cited by 10 publications

(17 citation statements)

References 37 publications

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“…4A, B ). Similarly, the serum opacity factor-induced remodeling of HDL has been shown to exhibit an enhanced ability to promote cholesterol effl ux ( 50 ). Using mast cell chymase, which selectively and completely depleted pre ␤ -HDL in acidic pH-modifi ed HDL ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Spontaneous remodeling of HDL particles at acidic pH enhances their capacity to induce cholesterol efflux from human macrophage foam cells

Nguyen

Öörni

Lee-Rueckert

et al. 2012

Journal of Lipid Research

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Section: Discussionmentioning

confidence: 99%

Spontaneous remodeling of HDL particles at acidic pH enhances their capacity to induce cholesterol efflux from human macrophage foam cells

Nguyen

Öörni

Lee-Rueckert

et al. 2012

Journal of Lipid Research

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“…To activate cells and elicit the macrophage phenotype, phorbol myristate acetate (PMA) (Sigma, St. Louis, Missouri, USA) was added to the cell media to a final concentration of 100ng/mL for 72 h. Cholesterol efflux was assayed as described previously. 20, 21 In brief, cells were seeded and grown for 24 h, then labeled in serum-containing medium with [1α,2α(n)- 3 H]cholesterol (specific radioactivity 1.81TBq/mmol, final radioactivity 74 KBq/mL) for 48 h at 37 °C in a 5% CO 2 incubator at which time they were ~ 80% confluent. After labeling, cells were washed twice with Ca 2+ /Mg 2+ free PBS to remove excess label, and incubated for an additional 18 h in serum-free medium (SFM) to ensure equilibration of labeled cholesterol into all intracellular pools.…”

Section: Methodsmentioning

confidence: 99%

Modest diet-induced weight loss reduces macrophage cholesterol efflux to plasma of patients with metabolic syndrome

Vasudevan

Tchoua

Gillard

et al. 2013

Journal of Clinical Lipidology

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BACKGROUND Obesity-linked metabolic syndrome (MetS) is associated with a dyslipidemic profile that includes hypertriglyceridemia and low plasma high-density lipoprotein cholesterol (HDL-C). HDL initiates reverse cholesterol transport (RCT) via macrophage cholesterol efflux (MCE). Some hypothesize that dyslipidemic patients have impaired RCT. MCE to patient plasma, a metric of HDL function, inversely correlates with atherosclerotic burden. Paradoxically, MCE to plasma of hypertriglyceridemic subjects is higher than that to normolipidemic (NL) plasma. OBJECTIVE Although weight-loss reduces dyslipidemia, its effect on MCE to the plasma of obese, MetS patients is unknown. Thus, we tested the hypothesis that reducing dyslipidemia with weight-loss reduces the MCE capacity of MetS plasma to that of NL plasma. METHODS Cholesterol efflux (MCE) from THP-1 macrophages to plasma from NL controls and to obese, MetS patients before and after weight-loss was measured. RESULTS MCE to plasma of obese, MetS patients was higher than that to control plasma (p=0.006). Weight-loss in MetS patients (mean = −9.77 kg) reduced dyslipidemia, insulin resistance and systolic blood pressure. HDL-C was unchanged and apolipoprotein A-I decreased with weight-loss. Weight-loss in MetS patients normalized MCE (p<0.001) to that of NL subjects. MCE correlated with apolipoprotein B levels (r2 = 0.13 – 0.38). Chromatography showed that macrophage cholesterol initially associates with HDL but accumulates in apolipoprotein B-containing lipoproteins at later times. CONCLUSIONS While the initial acceptor of macrophage cholesterol efflux is HDL, the elevated apo B lipoproteins are a cholesterol sink that increase MCE in MetS patients. Weight loss results in decreased apo B-lipoproteins and decreased MCE to plasma of MetS patients.

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“…Detailed metabolic studies demonstrate that multiple steps in reverse cholesterol transport from macrophages are inhibited in infl amed mice ( 21,22 ). Furthermore, proteins cotransported with HDL in plasma, such as paraoxonase and clusterin, have been proposed to have antioxidant and anti-infl ammatory properties, and their levels change in response to infl ammation ( 15,(24)(25)(26)(27). Loss of sterol effl ux capacity and of anti-infl ammatory and/or antioxidant proteins, perhaps in concert with gain of pro-infl ammatory proteins, may thus be key factors in generating dysfunctional HDL ( 7 ).…”

Section: Lc-ms/ms Analysismentioning

confidence: 99%

Inflammatory remodeling of the HDL proteome impairs cholesterol efflux capacity

Vaisar

Tang

Babenko

et al. 2015

Journal of Lipid Research

159

132

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Journal of Lipid Research Volume 56, 2015 1519have triggered intense interest in targeting HDL for therapeutic intervention. Several recent observations have cast doubt on the hypotheses that HDL-C levels relate to CAD risk in humans and that elevating HDL-C is therapeutic ( 3, 4 ). For example, genetic variations that alter levels of HDL-C do not always associate with CAD risk, and interventions that elevate HDL-C do not necessarily reduce cardiovascular events in humans with established CAD ( 5 ). Taken together, these observations indicate that HDL is complex and that simply quantifying HDL-C might be a poor way to assess HDL function ( 6, 7 ).The ability of HDL (or serum HDL, serum depleted of apoB-containing lipoproteins) to promote sterol effl ux from cultured macrophages incubated with radiolabeled cholesterol can vary markedly, despite similar levels of HDL-C and apoA-I ( 8 ). Therefore, HDL-C is not necessarily the major determinant of HDL's macrophage sterol effl ux capacity in this system. Importantly, the effl ux capacity of serum HDL is lower in individuals with prevalent CAD ( 9-11 ). A recent study of a large cohort, initially free of CAD, demonstrated that sterol effl ux associates strongly and negatively with the risk of future cardiac events ( 12 ). This association was strengthened by multivariate adjustment, suggesting that impaired HDL function affects incident cardiovascular risk by processes distinct from those involving HDL-C, LDL-cholesterol (LDL-C), and other traditional lipid risk factors. Together, these observations indicate that the sterol effl ux capacity of HDL might be a marker, and perhaps a mediator, of atherosclerotic Abstract Recent studies demonstrate that HDL's ability to promote cholesterol effl ux from macrophages associates strongly with cardioprotection in humans independently of HDL-cholesterol (HDL-C) and apoA-I, HDL's major protein. However, the mechanisms that impair cholesterol effl ux capacity during vascular disease are unclear. Infl ammation, a well-established risk factor for cardiovascular disease, has been shown to impair HDL's cholesterol effl ux capacity. We therefore tested the hypothesis that HDL's impaired effl ux capacity is mediated by specifi c changes of its protein cargo. Humans with acute infl ammation induced by low-level endotoxin had unchanged HDL-C levels, but their HDL-C effl ux capacity was signifi cantly impaired. Proteomic analyses demonstrated that HDL's cholesterol effl ux capacity correlated inversely with HDL content of serum amyloid A (SAA)1 and SAA2. In mice, acute infl ammation caused a marked impairment of HDL-C effl ux capacity that correlated with a large increase in HDL SAA. In striking contrast, the effl ux capacity of mouse infl ammatory HDL was preserved with genetic ablation of SAA1 and SAA2. Our observations indicate that the infl ammatory impairment of HDL-C effl ux capacity is due in part to SAA-mediated remodeling of HDL's protein cargo. -Vaisar, T

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Serum Opacity Factor Enhances HDL‐Mediated Cholesterol Efflux, Esterification and Anti Inflammatory Effects

Cited by 10 publications

References 37 publications

Spontaneous remodeling of HDL particles at acidic pH enhances their capacity to induce cholesterol efflux from human macrophage foam cells

Spontaneous remodeling of HDL particles at acidic pH enhances their capacity to induce cholesterol efflux from human macrophage foam cells

Modest diet-induced weight loss reduces macrophage cholesterol efflux to plasma of patients with metabolic syndrome

Inflammatory remodeling of the HDL proteome impairs cholesterol efflux capacity

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