Opposing effects of rheumatoid arthritis and low dose prednisolone on arginine metabolomics

Radhakutty, Anjana; Mangelsdorf, Brenda L.; Drake, Sophie M.; Rowland, Andrew; Smith, Malcolm D.; Mangoni, Arduino A.; Thompson, Campbell; Burt, Morton G.

doi:10.1016/j.atherosclerosis.2017.10.004

Cited by 21 publications

(20 citation statements)

References 47 publications

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“…Of interest, polyunsaturated acyl LPC and LPE presented an anti-inflammatory effect on animal models [60]. The effect of low dose GC (<10 mg/day) on arginine metabolism and cardiovascular risk in RA patients was also studied [61]. This study from Australia that included 36 RA patients, 18 of which were on GC (GC users) and 18 that were not receiving GC (non-GC-users), found that asymmetric dimethyl arginine (ADMA) and symmetric dimethyl arginine (SDMA) levels were lower in patients on chronic GC compared to non-GC users, suggesting that long-term treatment with GC had an improved endothelial function and a cardiovascular protective effect.…”

Section: Drugsmentioning

confidence: 99%

“…This study from Australia that included 36 RA patients, 18 of which were on GC (GC users) and 18 that were not receiving GC (non-GC-users), found that asymmetric dimethyl arginine (ADMA) and symmetric dimethyl arginine (SDMA) levels were lower in patients on chronic GC compared to non-GC users, suggesting that long-term treatment with GC had an improved endothelial function and a cardiovascular protective effect. by modulating arginine metabolism [61].…”

Section: Drugsmentioning

confidence: 99%

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Circulating Pro- and Anti-Inflammatory Metabolites and Its Potential Role in Rheumatoid Arthritis Pathogenesis

Coras

Murillo-Saich

Gumá

2020

Cells

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Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that affects synovial joints, leading to inflammation, joint destruction, loss of function, and disability. Although recent pharmaceutical advances have improved the treatment of RA, patients often inquire about dietary interventions to improve RA symptoms, as they perceive pain and/or swelling after the consumption or avoidance of certain foods. There is evidence that some foods have pro- or anti-inflammatory effects mediated by diet-related metabolites. In addition, recent literature has shown a link between diet-related metabolites and microbiome changes, since the gut microbiome is involved in the metabolism of some dietary ingredients. But diet and the gut microbiome are not the only factors linked to circulating pro- and anti-inflammatory metabolites. Other factors including smoking, associated comorbidities, and therapeutic drugs might also modify the circulating metabolomic profile and play a role in RA pathogenesis. This article summarizes what is known about circulating pro- and anti-inflammatory metabolites in RA. It also emphasizes factors that might be involved in their circulating concentrations and diet-related metabolites with a beneficial effect in RA.

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Section: Drugsmentioning

confidence: 99%

Section: Drugsmentioning

confidence: 99%

Circulating Pro- and Anti-Inflammatory Metabolites and Its Potential Role in Rheumatoid Arthritis Pathogenesis

Coras

Murillo-Saich

Gumá

2020

Cells

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“…Negative regulation of NO synthesis can also be mediated through overproduction of methylated arginine analogues such as ADMA. Recently, many clinical studies have demonstrated that plasma levels of ADMA were elevated in RA patients regardless of the presence of cardiovascular disease [55][56][57][58][59][60][61][62][63][64][65][66][67]. Furthermore, ADMA has been reported to be related to indices of endothelial dysfunction or subclinical atherosclerosis in some [56,65,68], but not all, conducted studies [58,60,61,67,68].…”

Section: Asymmetric Dimethylarginine (Adma)mentioning

confidence: 99%

“…Finally, it has been shown that TNF inhibitors improved the L-arginine/ADMA ratio due to the increase in L-arginine, and the L-arginine/ADMA ratio was longitudinally related to PWV after initiation of anti-TNF-α therapy [58]. Acute and chronic oral treatments with glucocorticoids have also different effects on arginine metabolites; while acute prednisolone therapy has no impact, chronic prednisolone treatment reduces ADMA and SDMA plasma concentrations [57].…”

Section: Rheumatoid Arthritis (Ra)mentioning

confidence: 99%

Role of the eNOS Uncoupling and the Nitric Oxide Metabolic Pathway in the Pathogenesis of Autoimmune Rheumatic Diseases

Łuczak

Madej

Kasprzyk

et al. 2020

Oxidative Medicine and Cellular Longevity

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Atherosclerosis and its clinical complications constitute the major healthcare problems of the world population. Due to the central role of endothelium throughout the atherosclerotic disease process, endothelial dysfunction is regarded as a common mechanism for various cardiovascular (CV) disorders. It is well established that patients with rheumatic autoimmune diseases are characterized by significantly increased prevalence of cardiovascular morbidity and mortality compared with the general population. The current European guidelines on cardiovascular disease (CVD) prevention in clinical practice recommend to use a 1,5-factor multiplier for CV risk in rheumatoid arthritis as well as in other autoimmune inflammatory diseases. However, mechanisms of accelerated atherosclerosis in these diseases, especially in the absence of traditional risk factors, still remain unclear. Oxidative stress plays the major role in the endothelial dysfunction and recently is strongly attributed to endothelial NO synthase dysfunction (eNOS uncoupling). Converted to a superoxide-producing enzyme, uncoupled eNOS not only leads to reduction of the nitric oxide (NO) generation but also potentiates the preexisting oxidative stress, which contributes significantly to atherogenesis. However, to date, there are no systemic analyses on the role of eNOS uncoupling in the excess CV mortality linked with autoimmune rheumatic diseases. The current review paper addresses this issue.

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“…This might account for the reduced coronary flow reserve, and consequent increased risk of ischaemic heart disease, reported in patients with rheumatoid arthritis and other similar autoimmune conditions [68]. In addition to the potential role of inflammatory pathways and traditional cardiovascular risk factors, the accumulation of the potent endogenous inhibitor of eNOS synthase, asymmetric dimethylarginine (ADMA), might also play a role in the pathogenesis of endothelial dysfunction in rheumatoid arthritis [69][70][71].…”

Section: Rheumatoid Arthritis: a Human Model Of Premature Vascular Agmentioning

confidence: 99%

Methotrexate and Vasculoprotection: Mechanistic Insights and Potential Therapeutic Applications in Old Age

Mangoni

Tommasi

Zinellu

et al. 2019

CPD

Self Cite

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Increasing age is a strong, independent risk factor for atherosclerosis and cardiovascular disease. Key abnormalities driving cardiovascular risk in old age include endothelial dysfunction, increased arterial stiffness, blood pressure, and the pro-atherosclerotic effects of chronic, low-grade, inflammation. The identification of novel therapies that comprehensively target these alterations might lead to a major breakthrough in cardiovascular risk management in the older population. Systematic reviews and meta-analyses of observational studies have shown that methotrexate, a first-line synthetic disease-modifying anti-rheumatic drug, significantly reduces cardiovascular morbidity and mortality in patients with rheumatoid arthritis, a human model of systemic inflammation, premature atherosclerosis, and vascular aging. We reviewed in vitro and in vivo studies investigating the effects of methotrexate on endothelial function, arterial stiffness, and blood pressure, and the potential mechanisms of action involved. The available evidence suggests that methotrexate might have beneficial effects on vascular homeostasis and blood pressure control by targeting specific inflammatory pathways, adenosine metabolism, and 5' adenosine monophosphate-activated protein kinase. Such effects might be biologically and clinically relevant not only in patients with rheumatoid arthritis but also in older adults with high cardiovascular risk. Therefore, methotrexate has the potential to be repurposed for cardiovascular risk management in old age because of its putative pharmacological effects on inflammation, vascular homeostasis, and blood pressure. However, further study and confirmation of these effects are essential in order to adequately design intervention studies of methotrexate in the older population.

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Opposing effects of rheumatoid arthritis and low dose prednisolone on arginine metabolomics

Cited by 21 publications

References 47 publications

Circulating Pro- and Anti-Inflammatory Metabolites and Its Potential Role in Rheumatoid Arthritis Pathogenesis

Circulating Pro- and Anti-Inflammatory Metabolites and Its Potential Role in Rheumatoid Arthritis Pathogenesis

Role of the eNOS Uncoupling and the Nitric Oxide Metabolic Pathway in the Pathogenesis of Autoimmune Rheumatic Diseases

Methotrexate and Vasculoprotection: Mechanistic Insights and Potential Therapeutic Applications in Old Age

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