High triglycerides and low high-density lipoprotein cholesterol lipid profile in rheumatoid arthritis: A potential link among inflammation, oxidative status, and dysfunctional high-density lipoprotein

Rodríguez‐Carrio, Javier; Alperi-López, Mercedes; López, Patricia; López‐Mejías, Raquel; Alonso-Castro, Sara; Abal, Francisco; Ballina-García, Francisco Javier

doi:10.1016/j.jacl.2017.05.009

Cited by 39 publications

(21 citation statements)

References 53 publications

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“…K/BxN arthritis at 21 weeks was also associated with reductions in total and HDL cholesterol (HDL-C) levels, similar to reports in active RA patients 15 More arthritic males had lower cholesterol levels compared to less arthritic females, and higher arthritic scores correlated significantly with lower cholesterol levels (Fig. 1 A).…”

Section: Resultssupporting

confidence: 81%

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Suppression of inflammatory arthritis in human serum paraoxonase 1 transgenic mice

Charles‐Schoeman

Wang

Shahbazian

et al. 2020

Sci Rep

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Paraoxonase 1(PON1) is an HDL-associated protein, which metabolizes inflammatory, oxidized lipids associated with atherosclerotic plaque development. Because oxidized lipid mediators have also been implicated in the pathogenesis of rheumatoid arthritis (RA), we evaluated the role of PON1 in murine inflammatory arthritis. K/BxN serum transfer (STIA) or collagen antibody transfer (CAIA) was used for arthritis induction in B6 mice homozygous for the PON1 human transgene [PON1Tg], PON1 knock-out mice [PON1KO], and wild type littermate control mice [WT]. Experiments were also performed in K/BxN mice with chronic arthritis, and in RA patients and healthy controls. Arthritis activity in K/BxN mice was associated with a marked dyslipidemia, lower PON1 activity and higher bioactive lipid mediators (BLM), as well as a dysregulated hepatic lipid gene expression profile. Higher serum PON1 activity correlated with lower BLM and lower arthritis activity in both K/BxN mice and RA patients. Overexpression of the human PON1 transgene was associated with reduced inflammatory arthritis, which correlated strongly with higher circulating PON1 activity, upregulation of the hepatic glutathione pathway, and reduction of circulating BLM. These results implicate PON1 as a potential novel therapeutic target for joint disease in RA with potential for vascular benefit, which warrants further investigation.

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Section: Resultssupporting

confidence: 81%

“…WT mice had suppression of TC and HDL-C, and increases in triglycerides (TG) after arthritis induction, similar to observations in patients with active RA 15 . In contrast, PON1Tg mice had no significant changes in TC or TG but increases in HDL-C after arthritis induction (Fig.…”

Section: Resultssupporting

confidence: 73%

Suppression of inflammatory arthritis in human serum paraoxonase 1 transgenic mice

Charles‐Schoeman

Wang

Shahbazian

et al. 2020

Sci Rep

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“…The serum concentration of cholesterol HDL (C-HDL) is only one of the markers of HDL particle number and has a feeble correlation with HDL functions. Multiple pathologic conditions, such as rheumatoid arthritis [ 89 ], hyperuricemia [ 90 , 91 ], diabetes mellitus [ 92 ], and acute coronary syndrome [ 93 ] trigger structural and functional alterations in HDL, becoming proinflammatory molecules. The above confirms that the function of HDL depends on its composition, such that alterations in its constituent enzymes and proteins result in changes in activity in conditions of oxidative stress, infection, and inflammation [ 78 , 94 ].…”

Section: Lipoproteins: Classes and Functionsmentioning

confidence: 99%

Current Therapies Focused on High-Density Lipoproteins Associated with Cardiovascular Disease

et al. 2018

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High-density lipoproteins (HDL) comprise a heterogeneous family of lipoprotein particles divided into subclasses that are determined by density, size and surface charge as well as protein composition. Epidemiological studies have suggested an inverse correlation between High-density lipoprotein-cholesterol (HDL-C) levels and the risk of cardiovascular diseases and atherosclerosis. HDLs promote reverse cholesterol transport (RCT) and have several atheroprotective functions such as anti-inflammation, anti-thrombosis, and anti-oxidation. HDLs are considered to be atheroprotective because they are associated in serum with paraoxonases (PONs) which protect HDL from oxidation. Polyphenol consumption reduces the risk of chronic diseases in humans. Polyphenols increase the binding of HDL to PON1, increasing the catalytic activity of PON1. This review summarizes the evidence currently available regarding pharmacological and alternative treatments aimed at improving the functionality of HDL-C. Information on the effectiveness of the treatments has contributed to the understanding of the molecular mechanisms that regulate plasma levels of HDL-C, thereby promoting the development of more effective treatment of cardiovascular diseases. For that purpose, Scopus and Medline databases were searched to identify the publications investigating the impact of current therapies focused on high-density lipoproteins.

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“…According to recent evidence, the state of low-grade systemic inflammation seems to be a key element in determining a condition of “accelerated” atherosclerosis [ 7 , 8 ]. Moreover, the chronic inflammation seems to be able to interfere with traditional CV risk factors such as lipoprotein metabolism, leading to quantitative and qualitative changes in triglycerides and low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol fractions [ 5 , 9 , 10 ]. Indeed, a condition of “reverse epidemiology” has been also taken into account for RA patients [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Lipids and Atherogenic Indices Fluctuation in Rheumatoid Arthritis Patients on Long-Term Tocilizumab Treatment

Cacciapaglia

Anelli

Rinaldi

et al. 2018

Mediators of Inflammation

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Rheumatoid arthritis (RA) patients are at high risk of cardiovascular (CV) events, and the chronic inflammatory state may generate quantitative and qualitative changes in lipoprotein fractions. The anti-IL-6 receptor tocilizumab (TCZ), even if effective in inflammation and joint damage prevention, determined significant alterations to RA patients' lipid levels in randomized controlled trials, but real-world data are lacking. We evaluated the changes in lipid fraction levels and disease activity in a longitudinal cohort of RA patients on long-term treatment with tocilizumab (TCZ) in a community setting. We retrospectively selected 40 naïve-biologic RA patients on treatment with intravenous TCZ compared to 20 RA patients on methotrexate treatment as the control group. Total cholesterol (Tot-Chol), low-density lipoproteins (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels were measured at the baseline and at 12, 24, and 52 weeks thereafter. At the same points, 28-joint disease activity score (DAS28), clinical disease activity index (CDAI), and EULAR clinical responses were also assessed. During the first 24 weeks, we observed in TCZ-treated patients a progressive statistically significant (p < 0.001) increase in Tot-Chol, LDL, HDL, and TG, which returned close to the baseline at 52 weeks. But no changes in the lipid-related CV risk indices Tot-Chol/HDL and LDL/HDL ratios and the atherogenic index (log10 TG/HDL) were detectable. Notably, we observed a statistically significant negative correlation between changes in lipid fractions and DAS28 or CDAI. The prolonged treatment with TCZ was associated to a transient increase in cholesterol's fractions during the first 6 months of treatment, with inverse correlation to disease activity, but with no impact on surrogate lipid indices of atherogenic risk. These findings may aid clinicians in interpreting the RA patient's lipid profile in daily clinical practice.

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High triglycerides and low high-density lipoprotein cholesterol lipid profile in rheumatoid arthritis: A potential link among inflammation, oxidative status, and dysfunctional high-density lipoprotein

Abstract: The TGHDL profile is associated with systemic inflammation, decreased PON1 activity, and poor clinical outcome on TNFα blockade in RA, suggesting a role of TRL and HDL dysfunction as the missing link between inflammation and lipid profile.

Cited by 39 publications

References 53 publications

Suppression of inflammatory arthritis in human serum paraoxonase 1 transgenic mice

Suppression of inflammatory arthritis in human serum paraoxonase 1 transgenic mice

Current Therapies Focused on High-Density Lipoproteins Associated with Cardiovascular Disease

Lipids and Atherogenic Indices Fluctuation in Rheumatoid Arthritis Patients on Long-Term Tocilizumab Treatment

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