Atheroprotective effects of methotrexate on reverse cholesterol transport proteins and foam cell transformation in human THP‐1 monocyte/macrophages

Reiss, Allison B.; Carsons, Steven E.; Anwar, Kamran; Rao, Soumya; Edelman, Sari D; Zhang, Hongwei; Fernández, Patricia; Cronstein, Bruce N.; Chan, Edwin S. L.

doi:10.1002/art.24040

Cited by 144 publications

(103 citation statements)

References 92 publications

(63 reference statements)

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“…An atheroprotective effect of MTX through A 2A receptor activation, which is involved in the facilitation of cholesterol outflow, was recently reported (30). In RA patients, the overexpression of A 3 adenosine receptor has been directly correlated with high levels of proinflammatory cytokines acting via up-regulation of NF-B, the DNA binding sites of which are present in the promoter of the A 3 receptor gene (31,32).…”

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confidence: 96%

Normalization of A_2A and A₃ adenosine receptor up‐regulation in rheumatoid arthritis patients by treatment with anti–tumor necrosis factor α but not methotrexate

Varani¹,

Massara²,

Vincenzi³

et al. 2009

Arthritis & Rheumatism

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Objective. To investigate A 1 , A 2A , A 2B , and A 3 adenosine receptors in lymphocytes and neutrophils from patients with early rheumatoid arthritis (ERA) as well as from RA patients treated with methotrexate (MTX) or anti-tumor necrosis factor ␣ (anti-TNF␣), as compared with those in age-matched healthy controls, and to examine correlations between the status and functionality of adenosine receptors and TNF␣ release and NF-B activation.Methods. Adenosine receptors were analyzed by saturation binding assays and Western blot analyses.

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mentioning

confidence: 96%

Normalization of A_2A and A₃ adenosine receptor up‐regulation in rheumatoid arthritis patients by treatment with anti–tumor necrosis factor α but not methotrexate

Varani¹,

Massara²,

Vincenzi³

et al. 2009

Arthritis & Rheumatism

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“…Во-вторых, посредством активизации аденозинового рецептора А2а, МТ уве-личивает обратный транспорт холестерина и ограничи-вает образование пенистых клеток в артериальной стен-ке. При этом пути реализации протективных эффектов МТ отличаются от механизма действия статинов и ан-титромботических препаратов [17,18]. Таким образом, по влиянию на сердечно-сосудистую систему МТ яв-ляется эталоном среди противовоспалительных пре-паратов [19][20][21].…”

Section: Discussionunclassified

Changes in serum lipids in patients with rheumatoid arthritis treated with a combination of tocilizumab and methotrexate compared with methotrexate alone for 24 weeks of observation

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Попкова

et al. 2015

Racionalʹnaâ farmakoterapiâ v kardiologii

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Научно-исследовательский институт ревматологии имени В.А. Насоновой 155522 Москва, Каширское шоссе д. 34ААктуальность. По данным литературы терапия тоцилизумабом (ТЦЗ) у больных ревматоидным артритом (РА) сопровождается ухудшением липидного профиля крови. Цель. Изучить динамику липидных параметров крови у больных РА на фоне комбинированной терапии ТЦЗ и метотрексатом (МТ) или монотерапии МТ при 24-не-дельном наблюдении. Материал и методы. В пилотное открытое нерандомизированнное 24-недельное исследование включено 72 пациента с достоверным диагнозом РА: 1) группа ТЦЗ+МТ (n=39; 30 женщин, медиана возраста 51 [43][44][45][46][47][48][49][50][51][52][53][54][55] лет; 6 внутривенных инфузий ТЦЗ по 8 мг/кг + МТ 10-20 мг/нед); 2) группа МТ (n=33; 23 женщины, медиана воз-раста 56 [48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63] лет; МТ 7,5-20 мг/нед). Результаты. Исходно в обеих группах наблюдался проатерогенный профиль крови. В группе МТ больше пациентов принимало статины (n=19; 57,6%), по сравне-нию с группой ТЦЗ+МТ (n=7; 18%), (p<0,05). Уровень липидов положительно коррелировал с традиционными факторами риска (p<0,05). Длительность и актив-ность РА отрицательно коррелировали с уровнем холестерина липопротеидов высокой плотности (ХС ЛПВП), (p<0,05). Через 24 нед в обеих группах наблюдался хо-роший/удовлетворительный противовоспалительный эффект терапии. В группе ТЦЗ+МТ уровень общего холестерина увеличился на 11%, ХС ЛПВП на 110%, индекс атерогенности (ИА) уменьшился на 47%, (p<0,05). В группе МТ уровень ХС ЛПВП повысился на 22%, ИА снизился на 16%, (p<0,05). У пациентов группы МТ, не при-нимавших статины, повысился как ХС ЛПВП на 24%, так и ХС неЛПВП на 27% (p<0,05), ИА значимо не изменился. У пациентов группы МТ, принимавших статины изолированно повысился ХС ЛПВП на 22%, ИА снизился на 37,3%, (p<0,05). Количество пациентов с достигнутыми целевыми уровнями сразу всех липидных пара-метров в обеих группах значимо не изменилось. Заключение. Комбинированная терапия ТЦЗ+МТ, как и монотерапия МТ, сопровождается положительной динамикой липидных параметров крови. Для достижения оптимального липидного профиля крови у больных РА требуется назначение адекватных доз статинов. Background. According to the some studies tocilizumab therapy (TCZ) in patients with rheumatoid arthritis (RA) is accompanied by deterioration of blood lipid profile. Aim. To study changes in serum lipid parameters in patients with RA treated with a combination of tocilizumab and methotrexate compared with methotrexate alone for 24 weeks of observation. Material and methods. Patients (n=72) with RA were included into the pilot non-randomized 24-week study and divided in two groups: 1) TCZ+MTX group (n=39; women -30; median age 51 [43][44][45][46][47][48][49][50][51][52][53][54][55] years; 6 i.v. infusions of TCZ 8 mg/kg + МТX 10-20 mg/week); 2) MTX group (n=33; women -23; mеdian age 56 [48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63] years; MTX 7.5-20 mg/week). Results. At the baseline, similar proatherogenic blood profile wa...

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“…Our finding is counterintuitive, because MTX has antiinflammatory effects due to its capacity to release adenosine. This increases the expression of enzymes involved in metabolizing cholesterol and of transporters involved in the reverse transport of cholesterol 52 .…”

Section: Discussionmentioning

confidence: 99%

Semiquantified Noncalcified Coronary Plaque in Systemic Lupus Erythematosus

2012

J Rheumatol

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Objective-A major cause of morbidity and mortality in systemic lupus erythematosus (SLE) is accelerated coronary atherosclerosis. New technology (computed tomographic angiography) can measure noncalcified coronary plaque (NCP), which is more prone to rupture. We report on a study of semiquantified NCP in SLE.Methods-Patients with SLE (n = 147) with no history of cardiovascular disease underwent 64-slice coronary multidetector computed tomography (MDCT). The MDCT scans were evaluated quantitatively by a radiologist, using dedicated software.Results-The group of 147 patients with SLE was 86% female, 70% white, 29% African American, and 3% other ethnicity. The mean age was 51 years. In our univariate analysis, the major traditional cardiovascular risk factors associated with noncalcified plaque were age (p = 0.007), obesity (p = 0.03; measured as body mass index), homocysteine (p = 0.05), and hypertension (p = 0.04). Anticardiolipin (p = 0.026; but not lupus anticoagulant) and anti-dsDNA (p = 0.03) were associated with higher noncalcified plaque. Prednisone and hydroxychloroquine therapy had no effect, but methotrexate (MTX) use was associated with higher noncalcified plaque (p = 0.0001). In the best multivariate model, age, current MTX use, and history of anti-dsDNA remained significant. Conclusion-Our results suggest that serologic SLE (anti-dsDNA) and traditional cardiovascular risk factors contribute to semiquantified noncalcified plaque in SLE. The association with MTX is not understood, but should be replicated in larger studies and in multiple centers. Key Indexing Terms SYSTEMIC LUPUS ERYTHEMATOSUS; CARDIOVASCULAR DISEASE; RISK FACTORS; COMORBIDITYCardiovascular disease, specifically from accelerated premature atherosclerosis, is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE) 1 . Patients with SLE are 2 to 9 times more likely than the general population to have myocardial infarctions 2,3,4 . The pathogenesis is multifactorial, including traditional cardiovascular risk factors, but also corticosteroids and inflammatory pathways 5,6,7,8 . The risk of an acute cardiac event is affected by the presence, extent, location, characteristics, and metabolic activity of coronary atherosclerotic plaque 13,14,15 . Noncalcified plaque may be more metabolically active than highly calcified plaque and preliminary data suggest that the presence of noncalcified or only partially calcified plaques is associated with greater risk of unstable presentation 16 . Motoyama, et al reported that the appearance of low attenuation plaque on multidetector CT was an independent predictor of acute coronary syndrome events for a 2-year followup period 17 . Noncalcified plaque may be present in the absence of coronary artery calcification: in a Japanese study, the prevalence of noncalcified plaque was 11.1% in patients with no coronary artery calcium and 23.4% in patients with mild coronary artery calcium 18 .In our previous study of noncalcified plaque in SLE, we found that 54% of patients with SLE h...

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Atheroprotective effects of methotrexate on reverse cholesterol transport proteins and foam cell transformation in human THP‐1 monocyte/macrophages

Cited by 144 publications

References 92 publications

Normalization of A_2A and A₃ adenosine receptor up‐regulation in rheumatoid arthritis patients by treatment with anti–tumor necrosis factor α but not methotrexate

Normalization of A_2A and A₃ adenosine receptor up‐regulation in rheumatoid arthritis patients by treatment with anti–tumor necrosis factor α but not methotrexate

Changes in serum lipids in patients with rheumatoid arthritis treated with a combination of tocilizumab and methotrexate compared with methotrexate alone for 24 weeks of observation

Semiquantified Noncalcified Coronary Plaque in Systemic Lupus Erythematosus

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Atheroprotective effects of methotrexate on reverse cholesterol transport proteins and foam cell transformation in human THP‐1 monocyte/macrophages

Cited by 144 publications

References 92 publications

Normalization of A2A and A3 adenosine receptor up‐regulation in rheumatoid arthritis patients by treatment with anti–tumor necrosis factor α but not methotrexate

Normalization of A2A and A3 adenosine receptor up‐regulation in rheumatoid arthritis patients by treatment with anti–tumor necrosis factor α but not methotrexate

Changes in serum lipids in patients with rheumatoid arthritis treated with a combination of tocilizumab and methotrexate compared with methotrexate alone for 24 weeks of observation

Semiquantified Noncalcified Coronary Plaque in Systemic Lupus Erythematosus

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Product

Resources

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Normalization of A_2A and A₃ adenosine receptor up‐regulation in rheumatoid arthritis patients by treatment with anti–tumor necrosis factor α but not methotrexate

Normalization of A_2A and A₃ adenosine receptor up‐regulation in rheumatoid arthritis patients by treatment with anti–tumor necrosis factor α but not methotrexate