| 1. |
- Berglund, S, et al.
(författare)
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Atherothrombotic events in rheumatoid arthritis are predicted by homocysteine : a six-year follow-up study
- 2009
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Ingår i: Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 27:5, s. 822-825
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to investigate whether homocysteine is linked to atherothrombotic (AT) events in patients with rheumatoid arthritis (RA). METHODS: Analysis of homocysteine (Hcy) levels was carried out in 235 consecutive RA patients. They were followed-up for 6.5 years or until death, with analysis of AT risk factors and the type and length of DMARD and corticosteroid treatment. The disease history before inclusion was collected. Six categories of AT events were defined. In addition, the diagnosis of the patients at follow-up was co-analyzed with the nationwide population-based Swedish Inpatient Register and Death Register to certify all events. RESULTS: The Hcy level was found to be higher in males (p<0.05) and increased with age (p<0.001). Patients with folic acid supplementation had significantly lower levels, while those on corticosteroids had higher levels. High Hcy levels predicted AT events (n=48) during a 6.5-year follow-up adjusted for age and male sex in a logistic regression analysis. CONCLUSION: In this study, RA patients on folic acid had lower Hcy levels. High Hcy levels (in addition to age, sex and diabetes) predicted AT event prospectively.
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| 2. |
- Grimsholm, Ola, et al.
(författare)
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Observations favouring the occurrence of local production and marked effects of bombesin/gastrin-releasing peptide in the synovial tissue of the human knee joint : comparisons with substance P and the NK-1 receptor.
- 2008
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Ingår i: Neuropeptides. - : Elsevier BV. - 0143-4179 .- 1532-2785. ; 42:2, s. 133-145
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Tidskriftsartikel (refereegranskat)abstract
- We have previously shown that levels of the neuropeptides substance P (SP) and bombesin/gastrin-releasing peptide (BN/GRP) in blood and synovial fluid correlate with levels of pro-inflammatory cytokines in patients with rheumatoid arthritis (RA). It is well-established that SP is present in nerve endings in the synovium whilst the source of BN/GRP in human joints is completely unknown. Nor is it known whether GRP-receptors (GRP-R) are present in human synovial tissue. This study aimed to investigate the expression pattern of SP, BN/GRP and their receptors (NK-1R and GRP-R) in synovial tissue. Synovial tissue specimens from patients with RA or osteoarthritis (OA) were processed for immunohistochemistry, in situ hybridisation and ELISA. The results show the presence of BN/GRP, but not SP, in cells in the synovial tissue at both the protein and mRNA level. We did not find immunoreactive BN/GRP in nerve structures. NK-1R and GRP-R were also expressed at both protein and mRNA levels in cells associated with blood vessels and cells in the interstitial tissue. ELISA analyses revealed both SP and BN/GRP to be present in synovial tissue extracts and that synovial levels of SP were higher in RA patients than those with OA. Our results indicate that BN/GRP is produced by non-neuronal cells in the synovial tissue. Furthermore, both BN/GRP and SP may exert their effects on the synovial tissue through the respective receptors. These results suggest that BN/GRP and SP may modulate inflammation and vascular events, and possibly healing processes in the synovium. Finally, nerves should not be considered as the source of BN/GRP in synovial tissue although this peptide is presumably intimately involved functionally in synovial tissue, a previously unrecognised fact.
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| 3. |
- Ljung, Lotta, et al.
(författare)
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Interleukin-1 receptor antagonist is associated with both lipid metabolism and inflammation in rheumatoid arthritis
- 2007
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Ingår i: Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 25:4, s. 617-620
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is a relationship between cardiovascular morbidity, inflammatory activity, and changes in the lipid profile in rheumatoid arthritis (RA), although the mechanisms are not fully elaborated. Recent know-ledge that white adipose tissue (WAT) is a producer of immunologically and metabolically active substances gives another perspective to study.OBJECTIVE: To evaluate the relationship between interleukin-1 receptor antagonist (IL-1Ra) and variables associated with WAT and inflammation in RA.METHODS: Anthropometric, inflammatory and metabolic variables were assessed in 23 women with RA and 23 matched controls. Spearman, partial correlation and factor analyses were performed.RESULTS: Inflammatory markers were increased in patients. In both groups, IL-1Ra correlated with leptin independent of age and BMI. IL-1Ra also correlated with haptoglobin and apolipoprotein (Apo) B in patients and with soluble TNF receptor (sTNFR) 1 in controls. In factor analysis, three latent factors were identified among patients. The first loaded on IL-1Ra, leptin, BMI, ApoB and body fat content (BF%), the second loaded on IL1-Ra and sTNF-receptors and the third showed inverse loadings on ApoA-I together with loadings on ESR, haptoglobin, orosomucoid, BF% and BMI.CONCLUSION: IL-1Ra was associated with markers of inflammation and with fat-related factors in RA patients, suggesting a dualistic relationship of IL-1Ra in RA. IL-1Ra correlated independently with leptin in both patients and controls, indicating a relationship between inflammation and leptin.
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| 4. |
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| 5. |
- Wållberg-Jonsson, Solveig, et al.
(författare)
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Increased arterial stiffness and indication of endothelial dysfunction in long-standing rheumatoid arthritis
- 2008
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Ingår i: Scandinavian Journal of Rheumatology. - : Taylor & Francis. - 0300-9742 .- 1502-7732. ; 37:1, s. 1-5
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Atherosclerotic progression is accelerated in rheumatoid arthritis (RA). We evaluated arterial stiffness and endothelial dysfunction in RA patients and controls by pulse wave analysis (PWA).Methods: Thirty RA patients with long‐standing disease and 30 age‐ and sex‐matched controls were examined using applanation tonometry of the radial artery before and after vasodilation by terbutaline (endothelium dependent) and nitroglycerin (endothelium independent). The aortic augmentation index (AIx) and time to reflected wave (transit time, Tr) were measured. Using the peripheral pulse curve, the stiffness index (SI) and the reflectance index (RI) were calculated. Tr and SI predominantly reflect large artery stiffness, whereas Aix and RI also reflect small vessel resistance. The PWA measurements were assessed in relation to adhesion molecules [soluble platelet endothelial cell adhesion molecule‐1 (sPECAM‐1), soluble vascular cell adhesion molecule‐1 (sVCAM‐1) and soluble intracellular adhesion molecule‐1 (sICAM‐1)], selectins (E, L and P), and inflammation [erythrocyte sedimentation rate (ESR), haptoglobin, interleukin (IL)‐6, IL‐1 receptor antagonist (IL‐1‐Ra), IL‐2‐soluble receptor (IL‐2sR), and tumour necrosis factor receptors‐I and ‐II (TNFR‐I and TNFR‐II)].Results: RA patients had shorter Tr (p<0.05) and higher SI (p<0.001) than controls, indicating impaired large vessel compliance. After terbutaline, Tr remained shorter (p<0.05), while SI (p<0.01) and AIx (p<0.01) were higher. The post‐terbutaline changes in AIx and RI (ΔAIx, ΔRI), suggested to be the best PWA measurements of endothelial function, were smaller in RA patients (p = 0.06). In RA, L‐selectin and sVCAM‐1 correlated with ΔRI and L‐selectin also with ΔAIx. Both RI and AIx correlated at baseline with a retrospective inflammatory activity score.Conclusion: Arterial stiffness was increased in RA patients. Endothelial dysfunction was implicated and correlated with levels of soluble adhesion molecules. Small vessel resistance correlated with the long‐standing inflammatory load in RA.
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| 6. |
- Ärlestig, Lisbeth, 1954-, et al.
(författare)
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Polymorphism of genes related to cardiovascular disease in patients with rheumatoid arthritis
- 2007
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Ingår i: Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 25:6, s. 866-871
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To analyze candidate genes, related to cardiovascular disease (CVD) in general, and potentially involved in the inflammatory process, in RA patients from northern Sweden. METHODS: Four hundred and sixty-seven individuals (345 females; 122 males) with RA (ACR criteria), having a mean age of 61.8 +/- 13.0 years and mean disease duration of 16.2 +/- 12.1 years, were consecutively recruited and followed-up for 3 years. The prevalence of CVD, [(ischemic heart disease (IHD), deep vein thromboses/pulmonary embolism (DVT/PE) and/or stroke/TIA] and hypertension was registered. Candidate genes encoding for Beta-fibrinogen (G-455A), Factor XIIIA (Val34Leu), plasminogen activator inhibitor type-1 (PAI-1 4G/5G), and tumor necrosis factor receptor (TNFR)II (M196R) were analysed. Controls (n = 672) were randomly selected according to age and gender from the Medical Biobank of Northern Sweden. Polymorphisms were genotyped using a TaqMan 9700HT and the 5'nuclease allelic discrimination assay. RESULTS: The genotypes, carriers and alleles did not differ in distribution between patients and controls. Carriage of the TNFRII R variant was more frequent among patients with hypertension (p = 0.018). The genotype distribution of PAI-1 in patients with IHD differed significantly (p = 0.002) because carriage of 4G was more frequent (p = 0.024). Combined carriage of TNFRII 196R variant and Beta-fibrinogen-455A was a stronger predictor for hypertension than each genotype separately. The distribution of FXIIIA genotypes deviated significantly in RA patients with DVT/PE (p = 0.028) with an increased frequency of the Leu34 variant. CONCLUSION: The unusual alleles of TNFRII, PAI-1 and FXIIIA were associated with CVD in RA patients. The combination of several of the rare types further increased the predictive values for CVD.
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