Adjuvant-induced arthritis is a relevant model to mimic coronary and myocardial impairments in rheumatoid arthritis

Bordy, Romain; Moretto, Johnny; Devaux, Sylvie; Wendling, Daniel; Moretto-Riedweg, Karena; Demougeot, Céline; Totoson, Perle

doi:10.1016/j.jbspin.2020.09.001

Cited by 7 publications

(8 citation statements)

References 37 publications

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“…AIA is a reliable model to investigate ED in RA. Indeed, ED in AIA was reported to affect conductance and resistance vessels either of the peripheral or cerebral circulation [5,31,33], as observed in RA patients [3,4,34]. Using this model, the present study demonstrated that Tofacitinib administered from the first signs of arthritis fully prevented ED.…”

Section: Discussionsupporting

confidence: 65%

Tofacitinib improved peripheral endothelial dysfunction and brain‐derived neurotrophic factor levels in the rat adjuvant‐induced arthritis model

Totoson

Peyronnel

Quirié

et al. 2021

Fundamemntal Clinical Pharma

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This study aimed to explore the effect of Tofacitinib on endothelial dysfunction and cerebral levels of brain-derived neurotrophic factor (BDNF) in the adjuvant-induced arthritis (AIA) rat model. Tofacitinib (10 mg/kg twice a day) or vehicle was administered from the first signs of inflammation. Arthritis scores were daily monitored while other parameters including endothelial function assessed from aortic rings, radiographic scores, blood pressure, heart rate, circulating levels of triglycerides, cholesterol, and interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), IL-17A, and cerebral BDNF levels were determined after 3 weeks of treatment. A group of non-AIA rats served as controls. In AIA rats, as compared with vehicle, Tofacitinib significantly reduced arthritis and radiographic scores, decreased total cholesterol and low-density lipoprotein cholesterol (LDL-C), but changed neither blood pressure nor heart rate and proinflammatory cytokines levels. It also fully restored acetylcholine (Ach)-induced relaxation (p < 0.05) through increased nitric oxide (NO) synthase activity, reduced BH 4 deficiency and O 2 À production, decreased cyclo-oxygenase-2 (COX-2)/arginase activities, and enhanced endothelium-derived hyperpolarizing factor (EDHF) production. These effects translated into a decrease in atherogenic index and an elevation of BDNF levels in the prefrontal cortex (p < 0.05) and hippocampus (p < 0.001). The present study identified Tofacitinib as an efficient therapeutic option to reduce cardiovascular risk and improve BDNF-dependent cognition in arthritis. K E Y W O R D S arthritis, BDNF, peripheral endothelial dysfunction, Tofacitinib | INTRODUCTIONRheumatoid arthritis (RA), the most common systemic autoimmune disease, is characterized by a reduced life expectancy. Cardiovascular diseases (CVD), including myocardial infarction and stroke, are the main cause of premature mortality and sudden death in RA [1]. Evidence from clinical studies showed that endothelial dysfunction (ED), the "sine qua non" condition for atherosclerosis appearance, is the key promoter of CVD and as such is a seminal target for reducing cardiovascular (CV) risk in RA [2]. Clinical and preclinical studies indicated that ED affects the macrovasculature and microvasculature in RA, at the systemic and Perle Totoson and Celian Peyronnel contributed equally to this work.

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Section: Discussionsupporting

confidence: 65%

Tofacitinib improved peripheral endothelial dysfunction and brain‐derived neurotrophic factor levels in the rat adjuvant‐induced arthritis model

Totoson

Peyronnel

Quirié

et al. 2021

Fundamemntal Clinical Pharma

Self Cite

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“…In a separate study [ 76 ], Zhou et al reported susceptibility to cardiac systolic dysfunction and dilated cardiomyopathy in mice with collagen antibody-induced arthritis with enhanced cardiac inflammatory cell infiltration and increased inflammatory gene expression including TNF-α and IL-6 in isolated ventricular cardiomyocytes and cardiac fibroblasts. In adjuvant-induced arthritis in rats, evidence has been shown of cardiac hypertrophy and endothelial dysfunction in coronary arteries as well as an exacerbated response to ischemia-reperfusion injury [ 77 ]. Mokotedi et al [ 78 ] recently reported diastolic impairment in rats subjected to collagen-induced arthritis, which correlated with increased levels of circulating inflammatory cytokines.…”

Section: The Role Of Inflammation In Heart Failurementioning

confidence: 99%

“…Further elegant experiments led to the identification of a causal role for downregulation of the cardiac specific spliced form of Xpb1s in HFpEF pathogenesis as a result of S -nitrosylation of the unfolded response protein sensor IRE1α. Endothelial dysfunction is evident in both RA patients as well as in rodent models of RA [ 77 , 89 , 90 ]. Again, this is linked to eNOS uncoupling and reduced NO bioavailability as well as increased iNOS expression/activity and increased levels of the NOS inhibitor asymmetric dimethylarginine (ADMA) [ 91 , 92 , 93 , 94 ].…”

Section: The Role Of Inflammation In Heart Failurementioning

confidence: 99%

Cardiac Dysfunction in Rheumatoid Arthritis: The Role of Inflammation

Chen

Norling

Cooper

2021

Cells

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Rheumatoid arthritis is a chronic, systemic inflammatory disease that carries an increased risk of mortality due to cardiovascular disease. The link between inflammation and atherosclerotic disease is clear; however, recent evidence suggests that inflammation may also play a role in the development of nonischemic heart disease in rheumatoid arthritis (RA) patients. We consider here the link between inflammation and cardiovascular disease in the RA community with a focus on heart failure with preserved ejection fraction. The effect of current anti-inflammatory therapeutics, used to treat RA patients, on cardiovascular disease are discussed as well as whether targeting resolution of inflammation might offer an alternative strategy for tempering inflammation and subsequent inflammation-driven comorbidities in RA.

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“…This occurs because these individuals present a greater predisposition to infection, systemic complications and secondary collateral problems due to treatment. The main extra‐articular manifestations include skin, eye, lung, heart and cardiovascular system, blood, neurological alterations, vasculitis and amyloidosis, 4–6 and we previously demonstrated it in the kidney 7 …”

Section: Introductionmentioning

confidence: 94%

“…The pathophysiological mechanisms of RA extra‐articular damages may involve the renin–angiotensin system (RAS). In rats subjected to adjuvant‐induced arthritis (AIA), an experimental model that simulates RA, 17 there was an increment in the expression of angiotensin receptors subtype 1 (AT 1 ) and angiotensin‐converting enzyme (ACE) in aorta tissues, which increases the local action of angiotensin II (Ang II), thereby leading to the local oxidative stress as well as exacerbation of the hypertension, endothelial dysfunction and vascular hypertrophy 5,18 . In addition, in rat kidneys the density of both AT 1 receptor and G‐coupled protein receptor of Ang1‐7 (Mas) are significantly increased by the AIA‐related inflammatory process while the ratio of Mas/AT 1 is reduced 19 .…”

Section: Introductionmentioning

confidence: 99%

Angiotensin involvement in kidney injury induced by rheumatoid arthritis in rat

Carlos

Carvalho

Angeli

et al. 2021

Clin Exp Pharma Physio

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Renal injury induced by rheumatoid arthritis is not clear and may be related to the angiotensin II. We aim to investigate the adjuvant‐induced arthritis (AIA) injury in rat kidney, focusing the angiotensin II/AT1 pathway. Male Wistar rats were allocated in to three groups: Control, AIA and AIA plus losartan. The AIA was induced by injection of 100 µL of an emulsion of dissected Mycobacterium tuberculosis (50 mg/mL) on the paw. Treatment with losartan was initiated on the first day of immunization (daily subcutaneous injection, 1 mg/kg). After 60 days post immunization, we evaluated kidney function by plasma creatinine, urea and uric acid levels and creatinine depuration; kidney injury by apoptosis analysis and inflammation markers such as macrophages, transforming growth factor beta (TGF‐β) and inducible nitric oxide synthase (iNOS) expression; oxidative stress by plasma thiobarbituric acid reactive substances (TBARS); renal expression of angiotensin receptors subtype 1 (AT1) and 2 (AT2) and plasma concentration of angiotensin II. AIA rats showed elevated plasma levels of creatinine, urea, uric acid, TBARS and Ang II and reduced creatinine depuration, and enhanced kidney macrophage number, TGF‐β, caspase‐3, iNOS and AT1/AT2 receptors expression. The losartan reduced plasma creatinine and its clearance, reduced macrophages and the expression of TGF‐β and iNOS in renal tissues, and reduced plasma TBARS. We conclude that AIA causes kidney injury by a physiopathological mechanism that involves AT1 stimulation in renal tissue, elevating the presence of macrophages, the expression of TGF‐β and iNOS, as well the local oxidative stress, which contribute to renal function deterioration.

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Adjuvant-induced arthritis is a relevant model to mimic coronary and myocardial impairments in rheumatoid arthritis

Cited by 7 publications

References 37 publications

Tofacitinib improved peripheral endothelial dysfunction and brain‐derived neurotrophic factor levels in the rat adjuvant‐induced arthritis model

Tofacitinib improved peripheral endothelial dysfunction and brain‐derived neurotrophic factor levels in the rat adjuvant‐induced arthritis model

Cardiac Dysfunction in Rheumatoid Arthritis: The Role of Inflammation

Angiotensin involvement in kidney injury induced by rheumatoid arthritis in rat

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