Abnormal function of high‐density lipoprotein is associated with poor disease control and an altered protein cargo in rheumatoid arthritis

Charles‐Schoeman, Christina; Watanabe, Junji; Lee, Yuen Yin; Fürst, Daniel E.; Amjadi, Sogol; Elashoff, David; Park, Grace; McMahon, Maureen; Paulus, Harold E.; Fogelman, Alan M.; Reddy, Srinivasa T.

doi:10.1002/art.24802

Cited by 134 publications

(152 citation statements)

References 41 publications

(25 reference statements)

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“…In accordance with our fi ndings, previous studies suggested that antiatherogenic activities of HDL are inversely correlated with systemic infl ammation in rheumatoid arthritis patients (31)(32)(33). Moreover, a recent study has provided evidence that autoantibodies against apoA-I contribute to reduced HDL levels in systemic lupus erythematosus patients, independently of hepatic HDL biogenesis.…”

Section: Discussionsupporting

confidence: 92%

Psoriasis alters HDL composition and cholesterol efflux capacity

Holzer

Wolf

Curcic

et al. 2012

Journal of Lipid Research

148

141

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This article is available online at http://www.jlr.org more than the skin ( 1 ). Traditional cardiovascular risk factors, such as hypertension, dyslipidemia, and obesity, are more frequent in psoriatic patients ( 2-4 ). However, even after adjusting for these risk factors, psoriasis has been shown to be associated with a higher incidence of myocardial infarction, stroke, and cardiovascular mortality ( 3,5,6 ). In moderate to severe psoriasis, a signifi cantly deteriorated lipid profi le was observed compared with healthy controls, with higher values of low-density lipoprotein, triglycerides, and signifi cantly decreased HDL levels ( 7 ).Recent studies clearly demonstrated that infl ammation impairs reverse cholesterol transfer in vivo ( 8, 9 ), providing evidence that infl ammation impairs HDL function. Emerging evidence suggests that assessment of HDL plasma concentrations alone is insuffi cient and indicate that the quality, rather than the mere quantity, of HDL determines its potential benefi cial effects against atherosclerosis ( 10 ). HDL is a complex lipoprotein particle with a broad variety of functions, also exerting atheroprotective activity via effects on the endothelium and by potent antiinfl ammatory capabilities ( 11-13 ). Recent studies have identifi ed HDL-associated proteins to be involved in the regulation of lipid metabolism, complement activation, growth-factor secretion, and proteolysis (14)(15)(16)(17)(18)(19).Functional impairment of HDL may contribute to the increased cardiovascular mortality experienced by psoriatic patients, but the impact of psoriasis on the composition and function of HDL has not been assessed. As qualitative alterations of HDL seem to be linked with increased cardiovascular complications, we hypothesized that HDL from psoriatic patients displays altered protein cargo and lipid composition, thereby rendering HDL dysfunctional.Abstract Psoriasis, a chronic infl ammatory skin disease, has been linked to increased myocardial infarction and stroke. Functional impairment of HDL may contribute to the excess cardiovascular mortality of psoriatic patients. However, data available regarding the impact of psoriasis on HDL composition and function are limited. HDL from psoriasis patients and healthy controls was isolated by ultracentrifugation and shotgun proteomics, and biochemical methods were used to monitor changed HDL composition. We observed a signifi cant reduction in apoA-I levels of HDL from psoriatic patients, whereas levels of apoA-II and proteins involved in acute-phase response, immune response, and endopeptidase/protease inhibition were increased. Psoriatic HDL contained reduced phospholipid and cholesterol. With regard to function, these compositional alterations impaired the ability of psoriatic HDL to promote cholesterol effl ux from macrophages. Importantly, HDLcholesterol effl ux capability negatively correlated with psoriasis area and severity index. We observed that control HDL, as well as psoriatic HDL, inhibited dihydrorhodamine (DHR) oxidation to a similar...

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Section: Discussionsupporting

confidence: 92%

Psoriasis alters HDL composition and cholesterol efflux capacity

Holzer

Wolf

Curcic

et al. 2012

Journal of Lipid Research

148

141

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“…Composition and functional characteristics of HDL are altered in RA. piHDL levels are increased in RA patients as compared to healthy controls (Hahn et al 2008) and correlate positively with disease activity (Charles-Schoeman et al 2009). Profound modifications of HDL composition in patients with active RA have been described, particularly with respect to protein content.…”

Section: Rheumatoid Arthritis (Ra)mentioning

confidence: 97%

Impact of Systemic Inflammation and Autoimmune Diseases on apoA-I and HDL Plasma Levels and Functions

Montecucco

Favari

Norata

et al. 2014

Handbook of Experimental Pharmacology

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The cholesterol of high-density lipoproteins (HDLs) and its major proteic component, apoA-I, have been widely investigated as potential predictors of acute cardiovascular (CV) events. In particular, HDL cholesterol levels were shown to be inversely and independently associated with the risk of acute CV diseases in different patient populations, including autoimmune and chronic inflammatory disorders. Some relevant and direct anti-inflammatory activities of HDL have been also recently identified targeting both immune and vascular cell subsets. These studies recently highlighted the improvement of HDL function (instead of circulating levels) as a promising treatment strategy to reduce inflammation and associated CV risk in several diseases, such as systemic lupus erythematosus and rheumatoid arthritis. In these diseases, anti-inflammatory treatments targeting HDL function might improve both disease activity and CV risk. In this narrative review, we will focus on the pathophysiological relevance of HDL and apoA-I levels/functions in different acute and chronic inflammatory pathophysiological conditions.

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“…To detect plasma esterase activities independently of ROSinduced fluorescence, we incubated the oxidized di-acetate form of DCFH (DCFDA), dissolved in methanol, with plasma under similar condition as were reported to monitor DCFHDA fluorescence. 30,[40][41][42][43] As shown in Figure 3(b), incubation of DCFDA with plasma rapidly resulted in a fluorescence signal indicative of a de-esterification reaction releasing the fluorescent DCF. To confirm that the increase in fluorescence was the result of the plasma-mediated released ....................................................................................................................... …”

Section: Dichlorofluorescein Fluorescence Assaysmentioning

confidence: 99%

Featured Article: Depletion of HDL₃high density lipoprotein and altered functionality of HDL₂in blood from sickle cell patients

Soupène¹,

Larkin²,

Kuypers³

2017

Exp Biol Med (Maywood)

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In sickle cell disease (SCD), alterations of cholesterol metabolism is in part related to abnormal levels and activity of plasma proteins such as lecithin cholesterol acyltransferase (LCAT), and apolipoprotein A-I (ApoA-I). In addition, the size distribution of ApoA-I high density lipoproteins (HDL) differs from normal blood. The ratio of the amount of HDL2 particle relative to the smaller higher density pre-β HDL (HDL3) particle was shifted toward HDL2. This lipoprotein imbalance is exacerbated during acute vaso-occlusive episodes (VOE) as the relative levels of HDL3 decrease. HDL3 deficiency in SCD plasma was found to relate to a slower ApoA-I exchange rate, which suggests an impaired ABCA1-mediated cholesterol efflux in SCD. HDL2 isolated from SCD plasma displayed an antioxidant capacity normally associated with HDL3, providing evidence for a change in function of HDL2 in SCD as compared to HDL2 in normal plasma. Although SCD plasma is depleted in HDL3, this altered capacity of HDL2 could account for the lack of difference in pro-inflammatory HDL levels in SCD as compared to normal. Exposure of human umbilical vein endothelial cells to HDL2 isolated from SCD plasma resulted in higher mRNA levels of the acute phase protein long pentraxin 3 (PTX3) as compared to incubation with HDL2 from control plasma. Addition of the heme-scavenger hemopexin protein prevented increased expression of PTX3 in sickle HDL2-treated cells. These findings suggest that ApoA-I lipoprotein composition and functions are altered in SCD plasma, and that whole blood transfusion may be considered as a blood replacement therapy in SCD. Impact statement Our study adds to the growing evidence that the dysfunctional red blood cell (RBC) in sickle cell disease (SCD) affects the plasma environment, which contributes significantly in the vasculopathy that defines the disease. Remodeling of anti-inflammatory high density lipoprotein (HDL) to pro-inflammatory entities can occur during the acute phase response. SCD plasma is depleted of the pre-β particle (HDL3), which is essential for stimulation of reverse cholesterol from macrophages, and the function of the larger HDL2 particle is altered. These dysfunctions are exacerbated during vaso-occlusive episodes. Interaction of lipoproteins with endothelium increases formation of inflammatory mediators, a process counteracted by the heme-scavenger hemopexin. This links hemolysis to lipoprotein-mediated inflammation in SCD, and hemopexin treatment could be considered. The use of RBC concentrates in transfusion therapy of SCD patients underestimates the importance of the dysfunctional plasma compartment, and transfusion of whole blood or plasma may be warranted.

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Abnormal function of high‐density lipoprotein is associated with poor disease control and an altered protein cargo in rheumatoid arthritis

Cited by 134 publications

References 41 publications

Psoriasis alters HDL composition and cholesterol efflux capacity

Psoriasis alters HDL composition and cholesterol efflux capacity

Impact of Systemic Inflammation and Autoimmune Diseases on apoA-I and HDL Plasma Levels and Functions

Featured Article: Depletion of HDL₃high density lipoprotein and altered functionality of HDL₂in blood from sickle cell patients

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Abnormal function of high‐density lipoprotein is associated with poor disease control and an altered protein cargo in rheumatoid arthritis

Cited by 134 publications

References 41 publications

Psoriasis alters HDL composition and cholesterol efflux capacity

Psoriasis alters HDL composition and cholesterol efflux capacity

Impact of Systemic Inflammation and Autoimmune Diseases on apoA-I and HDL Plasma Levels and Functions

Featured Article: Depletion of HDL3high density lipoprotein and altered functionality of HDL2in blood from sickle cell patients

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Featured Article: Depletion of HDL₃high density lipoprotein and altered functionality of HDL₂in blood from sickle cell patients