Remodeling of the HDL proteome with treatment response to abatacept or adalimumab in the AMPLE trial of patients with rheumatoid arthritis

Charles‐Schoeman, Christina; Gugiu, Gabriel B.; Ge, Helen Y.; Shahbazian, Ani; Lee, Y.Y.; Wang, X.; Fürst, Daniel E.; Ranganath, Veena K.; Maldonado, Michael A.; Lee, Terry; Reddy, Srinivasa T.

doi:10.1016/j.atherosclerosis.2018.04.003

Cited by 27 publications

(24 citation statements)

References 34 publications

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“…In patients with early RA, the treatment with various DMARD combinations improved HDL composition (paraoxonase 1 activity, haptoglobin, apoA1, myeloperoxidase) and anti-oxidant capacity, correlated with disease activity reduction [ 206 ]. Similar positive modifications in HDL quality were reported for the use of adalimumab and abatacept [ 207 ].…”

Section: Hdl Cec In Specific Conditionssupporting

confidence: 73%

High Density Lipoprotein Cholesterol Efflux Capacity and Atherosclerosis in Cardiovascular Disease: Pathophysiological Aspects and Pharmacological Perspectives

Adorni

Ronda

Bernini

et al. 2021

Cells

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Over the years, the relationship between high-density lipoprotein (HDL) and atherosclerosis, initially highlighted by the Framingham study, has been revealed to be extremely complex, due to the multiple HDL functions involved in atheroprotection. Among them, HDL cholesterol efflux capacity (CEC), the ability of HDL to promote cell cholesterol efflux from cells, has emerged as a better predictor of cardiovascular (CV) risk compared to merely plasma HDL-cholesterol (HDL-C) levels. HDL CEC is impaired in many genetic and pathological conditions associated to high CV risk such as dyslipidemia, chronic kidney disease, diabetes, inflammatory and autoimmune diseases, endocrine disorders, etc. The present review describes the current knowledge on HDL CEC modifications in these conditions, focusing on the most recent human studies and on genetic and pathophysiologic aspects. In addition, the most relevant strategies possibly modulating HDL CEC, including lifestyle modifications, as well as nutraceutical and pharmacological interventions, will be discussed. The objective of this review is to help understanding whether, from the current evidence, HDL CEC may be considered as a valid biomarker of CV risk and a potential pharmacological target for novel therapeutic approaches.

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Section: Hdl Cec In Specific Conditionssupporting

confidence: 73%

High Density Lipoprotein Cholesterol Efflux Capacity and Atherosclerosis in Cardiovascular Disease: Pathophysiological Aspects and Pharmacological Perspectives

Adorni

Ronda

Bernini

et al. 2021

Cells

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“…The longitudinal design of our study allowed us to clarify whether the effect of different drugs on lipid levels is related to the improvement of disease activity or there is a specific effect of these drugs. This question was raised for different drugs in several clinical trials [39,59,60]. Our data suggest that methotrexate, abatacept, and probably leflunomide may exert a beneficial effect upon HDL-C levels that would be independent of the improvement of disease activity, although the size of the effect of these treatments seems to be low.…”

Section: Discussionmentioning

confidence: 80%

Effects of disease activity on lipoprotein levels in patients with early arthritis: can oxidized LDL cholesterol explain the lipid paradox theory?

et al. 2020

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Background An increased risk of cardiovascular (CV) complications has been described in patients with rheumatoid arthritis (RA). It is the result of the combined effect of classic CV risk factors and others that are specific to the disease. Methods We assessed data from 448 early arthritis (EA) patients: 79% women, age (median [p25-p75]) at onset: 55 [44–67] years and disease duration at study entry 5 [3–8] months; and 72% fulfilled the 1987 RA criteria at 2 years of follow-up. Rheumatoid factor was positive in 54% of patients and anti-citrullinated peptide antibodies in 50%. The follow-up of patients ranged from 2 to 5 years with more than 1400 visits with lipoprotein measurements available (mean 2.5 visits/patient). Demographic- and disease-related variables were systematically recorded. Total cholesterol (TC), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) levels were obtained from routine laboratory tests. Oxidized-LDL (oxLDL-C) levels were assessed using a commercial ELISA kit. We fitted population-averaged models nested by patient and visit to determine the effect of independent variables on serum levels of TC, its fractions, and oxLDL-C. Results After adjustment for several confounders, high-disease activity was significantly associated with decreased TC, HDL-C, and LDL-C levels and increased oxLDL-C levels. Standardized coefficients showed that the effect of disease activity was greater on oxLDL-C and HDL-C. Interestingly, we observed that those patients with lower levels of LDL-C showed higher oxLDL-C/LDL-C ratios. Conclusions High-disease activity in EA patients results in changes in the HDL-C and oxLDL-C levels, which in turn may contribute to the increased risk of CV disease observed in these patients.

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“…HDL isolated from patients with rheumatoid arthritis, systemic lupus erythematosus, and antiphospholipid syndrome also display widespread structural changes, resulting in a pro-inflammatory phenotype that worsens as systemic inflammatory burden increases [69, 91]. Treatment with anti-inflammatory medications in these patients may partially reverse these structural and functional modifications, as evidenced by decreases in SAA and LBP content, increased NO bioavailability and PON-1 activity, and decreased SO production in individuals with rheumatoid arthritis treated with the monoclonal antibodies infliximab and adalimumab [99, 100].…”

Section: Hdl Function In Clinical Populations: Implications For Cvd Riskmentioning

confidence: 99%

High-Density Lipoprotein Function and Dysfunction in Health and Disease

Chiesa¹,

Charakida

2019

Cardiovasc Drugs Ther

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High-density lipoprotein cholesterol (HDL-c) has long been referred to as ‘good cholesterol’ due to its apparent inverse relationship with future CVD risk. More recent research has questioned a causal role for HDL-c in this relationship, however, as both genetic studies and numerous large-scale randomised controlled trials have found no evidence of a cardiovascular protective effect when HDL-c levels are raised. Instead, focus has switched to the functional properties of the HDL particle. Evidence suggests that both the composition and function of HDL may be significantly altered in the context of an inflammatory milieu, transforming the particle from a vasoprotective anti-atherogenic particle to a noxious pro-atherogenic equivalent. This review will summarise evidence relating HDL to CVD risk, explore recent evidence characterising changes in the composition and function of HDL that may occur in chronic inflammatory diseases, and discuss the potential for future HDL-modifying therapeutic interventions.

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Remodeling of the HDL proteome with treatment response to abatacept or adalimumab in the AMPLE trial of patients with rheumatoid arthritis

Cited by 27 publications

References 34 publications

High Density Lipoprotein Cholesterol Efflux Capacity and Atherosclerosis in Cardiovascular Disease: Pathophysiological Aspects and Pharmacological Perspectives

High Density Lipoprotein Cholesterol Efflux Capacity and Atherosclerosis in Cardiovascular Disease: Pathophysiological Aspects and Pharmacological Perspectives

Effects of disease activity on lipoprotein levels in patients with early arthritis: can oxidized LDL cholesterol explain the lipid paradox theory?

High-Density Lipoprotein Function and Dysfunction in Health and Disease

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