Proteomic profiling following immunoaffinity capture of high‐density lipoprotein: Association of acute‐phase proteins and complement factors with proinflammatory high‐density lipoprotein in rheumatoid arthritis

Watanabe, Junji; Charles‐Schoeman, Christina; Miao, Yunan; Elashoff, David; Lee, Yuen Yin; Katselis, George; Lee, Terry D.; Reddy, Srinivasa T.

doi:10.1002/art.34363

Cited by 138 publications

(138 citation statements)

References 40 publications

(69 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

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

141

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“…24,31,32,38 These associations indicate that HDL remodeling might not only contribute to disease characteristics but might also play a crucial role in disease progression. 39 Our data revealed that although a general recovery of protein distribution seems to occur in transplant patients with functioning grafts, individual proteins remain to be enriched, signifying a unique molecular composition of uremic HDL after transplantation.…”

Section: Discussionmentioning

confidence: 99%

“…It is now well established that the molecular composition of HDL strongly correlates with its functions and that its atheroprotective properties are severely impaired in different disease settings, including chronic renal insufficiency. [30][31][32] We investigated whether HDL remains dysfunctional after renal transplantation, because systematic and detailed characterization of HDL from transplant recipients could provide critical information regarding possible causes for their high cardiovascular risk. Proteomic analysis identified a highly heterogeneous protein cargo among uremic HDL, which differs in the transplant population itself, demonstrated by the opposing distribution of proteins according to biologic functions between KTx good and KTx poor HDL.…”

Section: Discussionmentioning

confidence: 99%

Restoration of Renal Function Does Not Correct Impairment of Uremic HDL Properties

Kopecky¹,

Haidinger²,

Birner-Grünberger³

et al. 2015

Journal of the American Society of Nephrology

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Cardiovascular disease remains the leading cause of death in renal transplant recipients, but the underlying causative mechanisms for this important problem remain elusive. Recent work has indicated that qualitative alterations of HDL affect its functional and compositional properties in ESRD. Here, we systematically analyzed HDL from stable renal transplant recipients, according to graft function, and from patients with ESRD to determine whether structural and functional properties of HDL remain dysfunctional after renal transplantation. Cholesterol acceptor capacity and antioxidative activity, representing two key cardioprotective mechanisms of HDL, were profoundly suppressed in kidney transplant recipients independent of graft function and were comparable with levels in patients with ESRD. Using a mass spectroscopy approach, we identified specific remodeling of transplant HDL with highly enriched proteins, including a-1 microglobulin/bikunin precursor, pigment epithelium-derived factor, surfactant protein B, and serum amyloid A. In conclusion, this study demonstrates that HDL from kidney recipients is uniquely altered at the molecular and functional levels, indicating a direct pathologic role of HDL that could contribute to the substantial cardiovascular risk in the transplant population.

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“…As sensitivity of the instrumentation has increased, so has the number of proteins that are proposed to be associated with HDL. These studies included HDL samples isolated by traditional density ultracentrifugation ( 21-31 ), immunoaffi nity capture ( 32 ), size exclusion chromatography ( 33 ), and even anion-exchange and isoelectric focusing (S. M. Gordon and W. S. Davidson , unpublished observations). A summary of the key experimental details for each of these studies is given in Table 1 .…”

Section: Applications Of Modern Proteomics To Hdlmentioning

confidence: 99%