BNIP3 Mediates the Different Adaptive Responses of Fibroblast-like Synovial Cells to Hypoxia in Patients With Osteoarthritis and Rheumatoid Arthritis

2021 ◽  
Author(s):  
Deng Ran ◽  
Wang Yan ◽  
Bu Yanhong ◽  
Hong Wu
Keyword(s):  
Rheumatoid Arthritis ◽  
Flow Cytometry ◽  
Western Blot ◽  
Cell Survival ◽  
Redox Balance ◽  
Adaptation To Hypoxia ◽  
Synovial Cells ◽  
Adaptive Responses ◽  
Promote Cell Survival ◽  
The Difference

Abstract Background: Hypoxia is one of the important characteristics of synovial microenvironment in rheumatoid arthritis (RA), and it is very important in the process of synovial hyperplasia. Fibroblast-like synovial cells (FLSs) are relatively affected by hypoxia injury in cell survival, while FLSs from patients with RA (RA-FLSs) are particularly resistant to hypoxia-induced cell death. The purpose of this study was to evaluate whether FLSs in patients with osteoarthritis (OA) and RA-FLSs have the same adaptation to hypoxia. Methods: CCK-8, flow cytometry and BrdU were used to detect the proliferation of OA-FLSs and RA-FLSs under different oxygen concentrations. Apoptosis was detected by AV/PI, TUNEL and Western blot, mitophagy was observed by electron microscope and Western blot, mitochondrial state was detected by reactive oxygen species (ROS) and mitochondrial membrane potential by flow cytometry, BNIP3 and HIF-1α were detected by Western blot and RT-qPCR. The silencing of BNIP3 is achieved by stealth RNA system technology. Results: After hypoxia, the survival rate of OA-FLSs was reduced, and the proliferation activity of RA-FLSs was further increased. Hypoxia induced increased apoptosis and inhibited autophagy of OA-FLSs, but not in RA-FLSs. Hypoxia treatment led to a more lasting adaptive response. RA-FLSs showed a more significant increase in gene expression regulated by HIF-1α transcription. Interestingly, they showed higher BNIP3 expression than OA-FLSs, and showed stronger mitophagy and proliferation activities. The BNIP3 siRNA experiment in RA-FLSs confirmed the potential role of BNIP3 in the survival of FLSs. The inhibition of BNIP3 resulted in the decrease of cell proliferation and the decrease of mitophagy and the increase of apoptosis. Conclusion: In summary, RA-FLSs maintained redox balance through mitophagy to promote cell survival under hypoxia. The mitophagy of OA-FLSs was too little to maintain the redox balance of mitochondria, leading to apoptosis. The difference of mitophagy between OA-FLSs and RA-FLSs under hypoxia is mediated by the expression of BNIP3.

Effects of riluzole (RZ) and ionizing radiation (IR) in metabotropic glutamate receptor-1 (GRM1) positive human melanoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9083-9083
Author(s):  
C. Green ◽  
D. Schiff ◽  
A. Khan ◽  
S. Goyal ◽  
J. Goydos ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Western Blot ◽  
Cell Survival ◽  
Glutamate Receptor ◽  
Blot Analysis ◽  
Caspase 3 ◽  
Metabotropic Glutamate Receptor ◽  
Human Melanoma ◽  
Metabotropic Glutamate

9083 Background: Melanoma has long been known to be relatively radio-resistant. GRM1 is a metabotropic glutamate receptor that has been detected in human melanoma cell lines and biopsies. Riluzole (RZ), a glutamate release inhibitor, has been shown to arrest GRM1 positive human melanoma cells in G2/M and sub-G1 phases of the cell cycle. The purpose of this study was to determine if RZ enhances the lethal effects of IR in human melanoma. Methods: ATP luminescence assays were performed. Clonogenic assays were performed and cell survival curves generated. Cell cycle analysis was performed utilizing flow cytometry. Western blot analysis was performed utilizing cleaved PARP and caspase-3 antibodies as markers of apoptosis. Results: Luminescence assays revealed 25uM Riluzole to be the necessary concentration for clonogenic assays. At 2Gy, there was a 48% reduction (p≤0.05) in cell survival in RZ-treated cells. At 4 Gy, there was a 19% reduction (p≤0.05) in cell survival in RZ-treated cells. No differences were seen at 6 and 8 Gy. Cell cycle analysis showed that the combination of IR and RZ was superior to IR alone in increasing the number of cells in sub-G1, which represents apoptotic death. Western blot analysis showed that the combination of IR and RZ showed yielded increased cleaved PARP and caspase-3 activity when compared to IR alone. Conclusions: Riluzole is a FDA approved drug that has long been used in ALS. It is relatively non-toxic and crosses the blood brain barrier. Our data shows that Riluzole in combination with radiation eliminates the radio-resistant shoulder of the C8161 survival curve. RZ and IR, as combination therapy are more lethal than IR or RZ alone in human melanoma, as demonstrated by flow cytometry and WB analysis. This data has promising implications for melanoma patients with brain metastases. No significant financial relationships to disclose.

Mer Receptor Tyrosine Kinase Is Over-Expressed In and Contributes to Oncogenesis In Acute Myeloid Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1390-1390
Author(s):  
Alisa B. Lee-Sherick ◽  
Kristen M. Eisenman ◽  
Susan Sather ◽  
Deborah DeRyckere ◽  
Jennifer Schlegel ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Targeted Therapy ◽  
Tyrosine Kinase ◽  
Western Blot ◽  
Cell Survival ◽  
Cell Lines ◽  
Wild Type ◽  
Knock Down ◽  
Acute Myelogenous

Abstract Abstract 1390 The abnormal activation of tyrosine kinases in pediatric leukemias has been associated with a poor prognosis, and provides a potential focus for targeted therapy. Pediatric acute myelogenous leukemia (AML) is known to be particularly difficult to treat successfully. The development of therapy for AML targeted against a specific cancer-promoting signaling pathway would potentially allow for a more efficacious clinical response with less therapy-associated toxicity. The Mer Tyrosine Kinase (TK), a transmembrane receptor in the TAM family, is known to regulate intracellular pathways promoting cell survival and proliferation in a number of malignancies, but has not previously been explored in AML. We assessed the prevalence of Mer TK expression in AML. Western blot and flow cytometric analysis demonstrated aberrant expression of Mer TK in 80% (13 of 15) of AML cell lines. Similarly, greater than 85% (24 of 28) of samples from newly diagnosed pediatric AML patients expressed Mer TK on leukemic blasts. In addition, 5 of 6 pediatric patients with relapsed or refractory AML had increased or equivalent Mer expression by flow cytometry relative to diagnostic samples. To assess whether Mer plays a role in proliferation in AML, we investigated downstream signaling pathways in the Nomo-1 and Kasumi-1 AML cell lines. Phosphoarray and western blot analysis demonstrated increased phospho-Erk 1/2, phospho-Akt, phospho-mTOR and phospho-MSK1 following treatment with Gas6, the Mer ligand. These data demonstrate activation of pathways which are known to aid in malignant cell survival. To assess the effect of Mer TK inhibition on myeloblast phenotype, we used two different shRNA constructs to decrease expression of Mer by >50% in the Nomo-1 and Kasumi-1 cell lines. The ability of these cell lines to evade apoptosis was determined by flow cytometry following staining with propidium iodide and Yo-Pro-1-iodide. Compared to wild-type Nomo-1 and Kasumi-1, the cell lines expressing decreased levels of Mer demonstrated two to four times more apoptosis in response to serum starvation (p<0.5). Additionally, myeloblast proliferative capacity was assessed using methylcellulose colony forming assays. Compared to wild-type, the AML cell lines expressing reduced levels of Mer demonstrated a 40–70% decrease in total colony forming units (p<0.5). To explore how knockdown of Mer affects myeloblast survival in vivo, we used a mouse xenograft model. Sub-lethally irradiated NSG mice were injected intravenously with wild-type Nomo-1 or Mer knock-down Nomo-1 lines and tumor-free survival was determined. Kaplan-Meier curves were generated and demonstrated a statistically significant difference in survival between mice injected with wild-type Nomo-1 cells and those injected with a Nomo-1 Mer knock-down cell line (20 versus 43 days, p<0.1). These data demonstrate a role for Mer in acute myelogenous leukemogenesis in vivo and suggest that inhibition of Mer TK may have a clinically significant effect in patients as a targeted therapy in the treatment of human AML. Disclosures: No relevant conflicts of interest to declare.

scholarly journals KDM4B Overexpression Promotes the Growth, Migration, and Invasion of Rheumatoid Arthritis Fibroblast-Like Synoviocytes by Activating STAT3 Pathway

2021 ◽  
Author(s):  
Xin Zhang ◽  
He Nan ◽  
Jialong Guo ◽  
Jinyu Liu
Keyword(s):  
Rheumatoid Arthritis ◽  
Flow Cytometry ◽  
Western Blot ◽  
Inflammatory Diseases ◽  
Migration And Invasion ◽  
Control Group ◽  
Inflammatory Microenvironment ◽  
Stat3 Signaling ◽  
Fibroblast Like Synoviocytes ◽  
Invasion Assays

AbstractIn rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) present a unique aggressive phenotype and have a passive response to the inflammatory microenvironment, which are critical for the disease’s progression. KDM4B, as a histone demethylase, functions as an oncogenic factor in many cancers and is implicated in osteoclastogenesis as well as pro-inflammatory cytokine release in inflammatory diseases. However, the effects of KDM4B on RA FLS have not been reported. To investigate this issue, our study determined the expression of KDM4B in RA FLS using RT-qPCR and western blot. The effects of KDM4B on RA FLS viability, apoptosis, migration, and invasion were detected by MTT, flow cytometry, transwell migration, and invasion assays. Furthermore, the interaction of KDM4B with STAT3 signaling was studied by western blot, MTT, flow cytometry, transwell migration, and invasion assays. The experimental results showed that KDM4B expression was upregulated in RA synovial tissues and FLS as compared to healthy control tissues and normal FLS. Knockdown of KDM4B obviously suppressed RA FLS viability, migration and invasion, and induced apoptosis. In addition, knockdown of KDM4B in RA FLS decreased the expression of p-STAT3 and MMP-9 but increased cleaved caspase-3 expression compared with the control group. Moreover, KDM4B overexpression could promote cell growth, migration and invasion, and suppress apoptosis in RA FLS by activating STAT3 signaling. Therefore, these findings provide new insight for understanding the pathogenesis of RA and indicate that KDM4B may have a potential to be an effective therapeutic target for RA.

scholarly journals CircASH2L facilitates tumor-like biologic behaviours and inflammation of fibroblast-like synoviocytes via miR-129-5p/HIPK2 axis in rheumatoid arthritis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xia Li ◽  
Meiting Qu ◽  
Jie Zhang ◽  
Kuanyin Chen ◽  
Xianghui Ma
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Cycle ◽  
Flow Cytometry ◽  
Western Blot ◽  
Cell Cycle Progression ◽  
Circular Rna ◽  
Cycle Progression ◽  
Qrt Pcr ◽  
Cycle Arrest ◽  
Fibroblast Like Synoviocytes

Abstract Background Previous study showed that circular RNA Absent-Small-Homeotic-2--Like protein (circASH2L) was higher in rheumatoid arthritis (RA) patients. However, the roles and mechanisms of circASH2L in RA progression remain unclear. Methods Levels analysis was conducted using western blot and qRT-PCR. The proliferation, apoptosis, cell cycle progression, migration, invasiveness, and inflammation of RA fibroblast-like synoviocytes (RA-FLSs) were determined via MTT, flow cytometry, western blot, transwell, and ELISA assays. Results CircASH2L knockdown in RA-FLSs suppressed cell proliferative, migratory, and invasive capacities, triggered cell cycle arrest, promoted apoptosis, and inhibited inflammation. Mechanistically, circASH2L targeted miR-129-5p, and repression of miR-129-5p abolished the functions of circASH2L silencing on the growth, motility, and inflammation of RA-FLSs. Besides, miR-129-5p was found to directly target HIPK2, and suppressed the tumor-like biologic behaviors and inflammation of RA-FLSs via regulating HIPK2. Importantly, we proved that circASH2L could modulate HIPK2 expression via miR-129-5p. Conclusion CircASH2L promoted RA-FLS growth, motility, and inflammation through miR-129-5p/HIPK2 axis.

scholarly journals Additive Effects of VDBP and 1,25(OH)2D3 on the Viability and Apoptosis of Rheumatoid Arthritis Synovial Fibroblasts

2021 ◽  
Vol 11 ◽  
Author(s):  
Yeyong Zhang ◽  
Shufeng Li ◽  
Feng Zhuo ◽  
Hongxing Wang ◽  
Xiubin Geng ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Cycle ◽  
Flow Cytometry ◽  
Synovial Fluid ◽  
Synovial Fibroblasts ◽  
Synovial Cells ◽  
Additive Effects ◽  
Vitamin D Binding Protein ◽  
Synovial Tissues ◽  
Lower Expression

AimThis study is to investigate the additive effect of Vitamin D-binding protein (VDBP) and 1,25(OH)2D3 on the viability and apoptosis of synovial cells from patients with rheumatoid arthritis (RA).MethodsSynovial tissues and synovial fluid of patients with RA and osteoarthritis (OA) were collected. The expression of VDBP was analyzed with immunohistochemistry and ELISA. CCK-8 assay was applied to detect cell viability. Flow cytometry was used to analyze cell cycle and apoptosis.ResultsImmunohistochemical results showed that the expression of VDBP in the synovium of RA patients was significantly lower than that of OA (P&lt;0.05). Similarly, ELISA results presented a lower expression of VDBP in the synovial fluid of RA patients. The results of CCK-8 assay showed that both 1,25(OH)2D3 and VDBP significantly inhibited the viability of rheumatoid arthritis synovial fibroblasts (RASF) (P&lt;0.05). The treatment with 1,25(OH)2D3+VDBP led to more significantly inhibited viability of RASF, compared with 1,25(OH)2D3 alone (P&lt;0.05). The results of flow cytometry showed that 1,25(OH)2D3 and VDBP both promoted the apoptosis of RASF (P&lt;0.05) and 1,25(OH)2D3+VDBP led to a higher proportion of RASF apoptosis, compared with 1,25(OH)2D3 alone (P&lt;0.05). However, 1,25(OH)2D3 and VDBP had no significant effect on the cell cycle of RASF. Additionally, 1,25(OH)2D3 promoted the expression of VDBP in RASF, but not concentration-dependently.ConclusionVDBP is reduced in the synovial tissue and synovial fluid of RA patients and can inhibit viability of RASF and promote the apoptosis of RASF. The 1,25(OH)2D3 can upregulate the expression of VDBP in RASF. Additionally, VDBP can enhance the effects of 1,25(OH)2D3 on viability and apoptosis of RASF.

Knock-Down of TAZ Gene Expression: A Model of Barth Syndrome with Accelerated Apoptosis of Myeloid Progenitor Cells Improved upon Treatment with Caspase-Specific Inhibitor

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3558-3558
Author(s):  
Vahagn Makaryan ◽  
David C. Dale ◽  
Andrew A Aprikyan
Keyword(s):  
Flow Cytometry ◽  
Western Blot ◽  
Cell Survival ◽  
Progenitor Cells ◽  
Specific Inhibitor ◽  
Barth Syndrome ◽  
Loss Of Function ◽  
Knock Down ◽  
Myeloid Progenitor ◽  
Myeloid Progenitor Cells

Abstract Barth syndrome (BTHS) is an X-linked recessive disorder characterized by neutropenia, cardiac and skeletal myopathies, and growth retardation. The mortality is high due to progressive cardiomyopathy and/or overwhelming bacterial infections. The incidence of BTHS is estimated to be as high as 1 in 100,000, but it is still a poorly recognized disease. The majority of Barth patients have mutations in the tafazzin (G4.5 or TAZ) gene, most of which appear to truncate the tafazzin protein likely resulting in the loss of its function. Tafazzin is a phospholipid acyltransferase involved in remodeling cardiolipin, the main lipid of the inner mitochondrial membrane. As a result, BTHS patients exhibit reduced levels of total CL and accumulation of monolysocardiolipin. A drosophila model of the Barth syndrome was recently reported, but cellular or mouse models of this disorder are not yet available. The link between these metabolic defects triggered by TAZ mutations and neutropenia remains largely unknown. We hypothesized that TAZ mutations lead to the loss of function of tafazzin protein causing impaired cell survival of neutrophil precursors, reduced production of neutrophils and neutropenia. To test this hypothesis, we knocked down the expression of the tafazzin gene in human myeloid progenitor HL60 cells using TAZ-specific shRNA and examined its effect on cell survival. Four shRNAs specific to exons 4 through 7 of the TAZ gene were used for transfection of human myeloid progenitor HL60 cells that were later examined by flow cytometry and Western blot analyses. At least 2 of the shRNA constructs resulted in substantial down-regulation in the expression level of the tafazzin gene in transfected human myeloid progenitor cells as determined by Western blot and confirmed by RT-PCR using gene-specific and GAPDH-specific primers. Flow cytometry analysis of DIOC6-labeled cells revealed that knock-down of the TAZ gene expression was associated with a significantly elevated dissipation of mitochondrial membrane potential compared with control cells with scrambled shRNA ((p<0.0009, n=3). Apoptosis studies using flow cytometry analyses revealed a significant increase in proportion of apoptotic annexin-positive cells compared with control cells transfected with scrambled shRNA (p<0.0002, n=6). The observed increase in apoptosis in response to TAZ knock-down was caspase3-dependent as evidenced by Western blot analysis. Treatment of the cells with caspase-specific inhibitor zVAD-fmk significantly improved cell survival characteristics to near normal level as determined by flow cytometry (p<0.02, n=4), suggesting that caspase-specific inhibitors may represent potentially therapeutic agents for patients with Barth syndrome. Thus, these data demonstrate that the loss of function of the TAZ gene is cytotoxic to hematopoietic cells and suggest that severe neutropenia is due to accelerated apoptosis of myeloid progenitor cells.

FRI0004 SURFACE AMP DEAMINASE 2 AS A NOVEL REGULATOR MODIFYING THE EXTRACELLULAR ATP-ADENOSINE BALANCE THAT IS DIFFERENTIALLY EXPRESSED IN PATIENTS WITH RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 573.1-573
Author(s):  
L. Ehlers ◽  
A. Kuppe ◽  
A. Damerau ◽  
M. Kirchner ◽  
C. Strehl ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mass Spectrometry ◽  
Flow Cytometry ◽  
Western Blot ◽  
Cell Lines ◽  
Immune Cells ◽  
Surface Expression ◽  
Extracellular Atp ◽  
Healthy Controls ◽  
Golgi Transport

Background:Adenosine and its nucleotides represent crucial immunomodulators in the extracellular environment. ATP and ADP are released from stressed cells in states of inflammation, whereas adenosine serves as a key anti-inflammatory mediator1. The ectonucleotidases CD39 and CD73 are responsible for the sequential catabolism of ATP to adenosine via AMP, thereby promoting an anti-inflammatory milieu induced by the “adenosine halo”. Great importance has been attributed to these enzymes in the pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA) and as targets in cancer therapy2 3. AMPD2 mediates AMP deamination to IMP, thus constituting an ambiguous mediator both enhancing the degradation of inflammatory ATP and reducing the formation of protective adenosine. Here, we postulate that this pathway is also present on the cell surface of immune cells and modified under inflammatory conditions.Objectives:Therefore, we analysed surface AMPD2 expression and its modulation on distinct cell lines and primary immune cells.Figure 1.Surface AMPD2 as a novel regulator of the extracellular ATP-adenosine balance.Methods:Firstly, AMPD2 surface expression was verified by immunoprecipitation from membrane fractions isolated from cell lines (HEK293 and HMEC1) and CD14+ monocytes analysed by western blot and mass spectrometry. In addition, surface biotinylation of the aforementioned cells was performed. Also, AMPD2 surface expression was evaluated by flow cytometry, analysing both cell lines (HEK293, HMEC1, THP1, and Jurkat) and primary human immune cells from healthy donors and patients with RA.Secondly, co-expression of surface AMPD2, CD39 and CD73 on PBMCs was analysed by flow cytometry directly after isolation as well as after a 24h culture period. Moreover, surface expression was assessed after immunostimulation and Golgi transport inhibition.Results:AMPD2 surface expression was confirmed by western blot and mass spectrometry of (i) precipitated AMPD2 from membrane fractions and (ii) biotinylated surface molecules in HEK293 and HMEC1 as well as CD14+ monocytes. Surface expression was reduced after AMPD2 knockdown in HEK293. Flow cytometric analysis further verified AMPD2 surface expression and revealed a significant decrease after Golgi transport inhibition (p<0.01). TLR stimulation strongly enhanced the surface expression of AMPD2 and CD39 on monocytes (p<0.05), whereas dexamethasone at high therapeutic doses inversely affected AMPD2 surface expression on lymphocytes and monocytes (p<0.01). Analysis of AMPD2 surface expression on PBMCs from RA patients revealed higher expression levels compared to sex- and age-matched healthy controls (p<0.05).Conclusion:We demonstrate AMPD2 surface expression on immune cells for the first time. Hence, we reveal a novel regulator of the extracellular ATP-adenosine balance that is differentially expressed in RA patients compared to healthy controls. The extracellular conversion of AMP into IMP may constitute a shunt-like mechanism adding to the CD39-CD73 system controlling immunomodulation.References:[1]Regateiro FS, Cobbold SP, Waldmann H. CD73 and adenosine generation in the creation of regulatory microenvironments.Clinical and experimental immunology2013;171(1):1-7. doi: 10.1111/j.1365-2249.2012.04623.x[2]Morandi F, Horenstein AL, Rizzo R, et al. The Role of Extracellular Adenosine Generation in the Development of Autoimmune Diseases.Mediators of inflammation2018;2018:7019398. doi: 10.1155/2018/7019398[3]Allard B, Longhi MS, Robson SC, et al. The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets.Immunol Rev2017;276(1):121-44. doi: 10.1111/imr.12528Acknowledgments:This project is funded by an unrestricted grant by Horizon Pharma plc.Disclosure of Interests:Lisa Ehlers: None declared, Aditi Kuppe: None declared, Alexandra Damerau: None declared, Marieluise Kirchner: None declared, Cindy Strehl: None declared, Frank Buttgereit Grant/research support from: Amgen, BMS, Celgene, Generic Assays, GSK, Hexal, Horizon, Lilly, medac, Mundipharma, Novartis, Pfizer, Roche, and Sanofi., Timo Gaber: None declared

High disease activity is associated with higher blood pressure in recent onset rheumatoid arthritis patients, post-hoc analyses of IMPROVED study

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
M Gegenava ◽  
SA Bergstra ◽  
H Maassen ◽  
CF Allaart
Keyword(s):  
Rheumatoid Arthritis ◽  
Blood Pressure ◽  
Disease Activity ◽  
Classification Criteria ◽  
Recent Onset ◽  
American College Of Rheumatology ◽  
Cardiovascular Morbidity And Mortality ◽  
The Difference ◽  
Post Hoc ◽  
Acpa Status

Abstract Funding Acknowledgements Type of funding sources: None. Background Rheumatoid arthritis (RA) is a chronic autoimmune disease with a high prevalence of cardiovascular morbidity and mortality. Purpose: purpose of our project was to investigate the association between disease activity and systolic and diastolic blood pressure (SBP, DBP) in patients with recent-onset rheumatoid arthritis (RA 2010 criteria) or undifferentiated arthritis (UA) who were treated to target disease activity score (DAS)&lt;1.6 in the IMPROVED study. Methods: The associations between disease activity and SBP/DBP were tested for 610 patients (364 RA, 246 UA), cross-sectionally and over time. GEE analyses were performed with both SBP and DBP as outcome measures and disease activity categories (DAS&lt;1.6;&gt;1.6 but ≤2.4; &gt;2.4), CRP level, treatment arms or the number of visits on a certain drug as potential predictors in separate analyses. Separate analyses tested potential contributions of gender, anti-cyclic citrullinated peptide antibodies (ACPA) status, and fulfilling the 2010 ACR/EULAR (American college of rheumatology/ European league against rheumatism) classification criteria. In addition association of BP with various levels of disease activity was tested with T-test. Results: At the baseline mean (SD) SBP was 133 (20) and DBP mean (SD) was 80 (10).  SBP &gt; 140mm Hg was observed in 40% of patients and DBP &gt; 90 mm Hg  in 21% of patients. SBP and DBP statistically significantly decreased during 5 years follow up (mainly during year 1), but the difference in mm Hg was small. Estimates from GEE analysis showed that patients with high DAS &gt;2.4 (HDAS) had a statistically significantly higher SBP (average 3 mm Hg higher, 95% CI 1.7; 4.2, p &lt; 0.01), than the patients in with DAS ≤2.4. ANOVA analyses showed a statistically significant association between SBP and DAS. In addition, post hoc analyses showed that patients with HDAS had a statistically significantly higher  SBP (mean (SD) 132 (19) than the patients with DAS &lt; 1.6 (remission) (mean (SD) 129 (20), p &lt; 0.01), and patients in LDAS but DAS≥1.6 had a statistically significantly higher SBP (mean (SD) 131 (19) than the patients in remission (mean (SD)  129 (20), p = 0.02) (Figure 1), whereas no association was found between DAS category and DBP. Gender, ACPA status or fulfilling the 2010 classification criteria did not influence the relation between DAS and blood pressure. Conclusions: In patients with RA or UA, a higher DAS is associated with higher blood pressure, but the clinical impact is unclear. Abstract Figure 1

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