Chronic arthritis and cardiovascular disease: Altered blood parameters give rise to a prothrombotic propensity

BackgroundCanine atopic dermatitis (cAD) is a common chronic and pruritic skin disease in dogs. The development of cAD involves complex interactions between environmental antigens, genetic predisposition and a number of disparate cell types. The aim of the present study was to perform comprehensive analyses of peripheral blood of AD dogs in relation to healthy subjects in order to determine the changes which would be characteristic for cAD.ResultsThe number of cells in specific subpopulations of lymphocytes was analyzed by flow cytometry, concentration of chosen pro- and anti-inflammatory cytokines (IL-4, IL-10, IL-13, TNF-α, TGF-β1) was determined by ELISA; and microarray analysis was performed on RNA samples isolated from peripheral blood nuclear cells of AD and healthy dogs. The number of Th cells (CD3+CD4+) in AD and healthy dogs was similar, whereas the percentage of Tc (CD3+CD8+) and Treg (CD4+CD25+ Foxp3+) cells increased significantly in AD dogs. Increased concentrations of IL-13 and TNF-α, and decreased levels of IL-10 and TGF-β1 was observed in AD dogs. The level of IL-4 was similar in both groups of animals. Results of the microarray experiment revealed differentially expressed genes involved in transcriptional regulation (e.g., transcription factors: SMAD2, RORA) or signal transduction pathways (e.g., VEGF, SHB21, PROC) taking part in T lymphocytes lineages differentiation and cytokines synthesis.ConclusionsResults obtained indicate that CD8+ T cells, beside CD4+ T lymphocytes, contribute to the development of the allergic response. Increased IL-13 concentration in AD dogs suggests that this cytokine may play more important role than IL-4 in mediating changes induced by allergic inflammation. Furthermore, observed increase in Treg cells in parallel with high concentrations of TNF-α and low levels of IL-10 and TGF-β1 in the peripheral blood of AD dogs point at the functional insufficiency of Treg cells in patients with AD.Electronic supplementary materialThe online version of this article (doi:10.1186/s12917-016-0805-6) contains supplementary material, which is available to authorized users.

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“…Several studies have demonstrated that TNF-α inhibits activation of protein C, thereby affecting the coagulation process [68–70]. …”

Section: Discussionmentioning

confidence: 99%

Lymphocytic, cytokine and transcriptomic profiles in peripheral blood of dogs with atopic dermatitis

et al. 2016

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“…Carotid intima media thickness, endothelial dysfunction, MPV and EAT thickness are some parameters that suggested for evaluation of increased atherosclerotic risk [3-5,7]. Familial Mediterranean fever is an inflammatory disease suggested to predispose to atherosclerosis [4-6].…”

Section: Discussionmentioning

confidence: 99%

“…The possibility of atherosclerosis was reported to be increased in cases with rheumatic diseases [1,3]. Case-control studies allowing evaluation of carotid intima media thickness and endothelial dysfunction found a predisposition of FMF patients to atherosclerosis [4,5].…”

Section: Introductionmentioning

confidence: 99%

“…Case-control studies allowing evaluation of carotid intima media thickness and endothelial dysfunction found a predisposition of FMF patients to atherosclerosis [4,5]. Mean platelet volume (MPV) and epicardial adipose tissue (EAT) thickness are novel parameters used in prediction of the risk of atherosclerosis [3,6-8]. Albeit contradictory results have been reported, there are some studies investigating the usefulness of MPV in assessment of atherosclerotic risk in cases with FMF [6,9,10].…”

Section: Introductionmentioning

confidence: 99%

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Assessment of epicardial adipose tissue thickness and the mean platelet volume in children with familial Mediterranean fever

et al. 2015

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BackgroundFamilial Mediterranean fever (FMF) is an inflammatory disease, which is suggested to be associated with increased risk of atherosclerosis. Epicardial adipose tissue (EAT) thickness and the mean platelet volume (MPV) are parameters used in prediction of atherosclerotic risk in various conditions. These parameters were evaluated in children with FMF and compared with healthy controls.MethodsForty-five patients with FMF and 54 age- and gender-matched healthy controls were assessed. Duration of symptoms, age at diagnosis, duration of delay in diagnosis, frequency and duration of FMF attacks, disease severity scores, response to colchicine therapy, MEditerraneanFeVer (MEFV) gene mutations, and MPV values were recorded. EAT thicknesses were measured by echocardiography.ResultsEpicardial adipose tissue thicknesses of the children with FMF were found to be significantly greater than that of controls (5.1 ± 1.4 vs. 4.5 ± 0.9 mm, p = 0.036). FMF patients had significantly higher MPV values compared with the controls (7.8 ± 1.1 vs. 7.3 ± 1.4 fl, p = 0.044). Age at diagnosis, duration of delay in diagnosis, and MPV values were found to be correlated with EAT thickness in the patient group (r = 0.49, p = 0.001 for the former parameters and r = 0.32, p = 0.04 for MPV).ConclusionEpicardial adipose tissue thickness and MPV values seem to be increased in children with FMF. These findings may indicate an increased risk of atherosclerosis in FMF patients.

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“…84 This review did not focus on clinical endpoints, but instead subclinical measures, which can provide mechanistic insight. Thus, our results do not mean that anti-TNFα treatment could not result in an improvement in outcomes due to other mechanisms; for example, a reduction in prothrombotic tendency 85,86 or through improvement in quality of life facilitating lifestyle change. Furthermore, this study only addresses anti-TNFα biologics.…”

Section: Antibody Associated Systemic Vasculitismentioning

confidence: 59%

Do anti‐tumour necrosis factor‐α biologics affect subclinical measures of atherosclerosis and arteriosclerosis? A systematic review

Knowles

Nadeem

Chowienczyk

2020

Brit J Clinical Pharma

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Aims: Inflammatory cytokines, particularly tumour necrosis factor-α (TNFα), are thought to promote arterial disease through a variety of mechanisms leading to arteriosclerosis and atherosclerosis. We reviewed the existing evidence of the effect of anti-TNFα treatment on arteriosclerosis and atherosclerosis in chronic inflammatory disease. Methods:We performed a systematic review of studies examining effects of monoclonal antibodies against TNFα on subclinical measures of arteriosclerosis (arterial pulse wave velocity) and atherosclerosis (endothelial function measured by flowmediated dilation or forearm blood flow responses to endothelium-dependent agonists, and common carotid intima-media thickness). Results:We identified 60 studies (of 854 potential studies identified using a systematic search) in which effects of anti-TNFα biologics on these measures were assessed in patients receiving anti-TNFα therapy for a clinical indication (usually an inflammatory disease such as an inflammatory arthritis, psoriasis or inflammatory bowel disease). Of these, only 6 were randomised clinical controlled trials. Whilst many observational studies and noncontrolled studies reported positive findings, positive finding were reported in only 1 of 6 randomised clinical controlled trials. Conclusions:There is no strong evidence for an effect of anti-TNFα biologics on the subclinical measures of arteriosclerosis or atherosclerosis examined in this review.This does not exclude a positive effect of TNFα biologics on clinical outcomes through alternate pathways including those induced by remission of the primary inflammatory disease.

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Chronic arthritis and cardiovascular disease: Altered blood parameters give rise to a prothrombotic propensity

Abstract: This analysis provides a first identification of the mechanisms by which inflammatory arthritis can aggravate cardiovascular disease.

Cited by 44 publications

References 99 publications

Lymphocytic, cytokine and transcriptomic profiles in peripheral blood of dogs with atopic dermatitis

Lymphocytic, cytokine and transcriptomic profiles in peripheral blood of dogs with atopic dermatitis

Assessment of epicardial adipose tissue thickness and the mean platelet volume in children with familial Mediterranean fever

Do anti‐tumour necrosis factor‐α biologics affect subclinical measures of atherosclerosis and arteriosclerosis? A systematic review

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