34 results on '"Helseth, Ragnhild"'
Search Results
2. Gene expression of fibrinolytic markers in coronary thrombi
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Nordeng, Jostein, Solheim, Svein, Åkra, Sissel, Schandiz, Hossein, Hoffmann, Pavel, Roald, Borghild, Bendz, Bjørn, Arnesen, Harald, Helseth, Ragnhild, and Seljeflot, Ingebjørg
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- 2022
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3. Links Between Adipose Tissue Gene Expression of Gut Leakage Markers, Circulating Levels, Anthropometrics, and Diet in Patients with Coronary Artery Disease.
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Aune, Susanne Kristine, Helseth, Ragnhild, Kalstad, Are A, Laake, Kristian, Åkra, Sissel, Arnesen, Harald, Solheim, Svein, and Seljeflot, Ingebjørg
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BODY mass index ,ADIPOSE tissues ,CORONARY artery disease ,DIETARY patterns ,GENE expression ,LEAKAGE ,BUTTOCKS - Abstract
Background: Recent studies suggest gut-derived lipopolysaccharide (LPS)-translocation to play a role in both systemic inflammation and in inflammatory adipose tissue. We aimed to investigate whether circulating LPS-related inflammatory markers and corresponding genetic expression in adipose tissue were associated with obesity, cardiometabolic risk factors, and dietary habits in patients with coronary artery disease. Methods: Patients (n=382) suffering a myocardial infarction 2– 8 weeks prior to inclusion were enrolled in this cross-sectional study. Subcutaneous adipose tissue (SAT), taken from the gluteal region, and fasting blood samples were collected at inclusion for determination of genetic expression of LPS-binding protein (LBP), CD14, toll-like receptor 2 (TLR2), and TLR4 in SAT, and LPS, LBP, and soluble cluster of differentiation 14 (sCD14) in the circulation. All patients filled out a dietary registration form. Results: Patients (median age 74 years, 25% women), had a median body mass index (BMI) of 25.9 kg/m
2 . Circulating levels of LBP correlated to BMI (p=0.02), were significantly higher in overweight or obese (BMI≥ 25 kg/m2 ) compared to normal- or underweight patients (BMI< 25 kg/m2 ), and were significantly elevated in patients with T2DM, hypertension, and MetS, compared to patients without (p≤ 0.04, all). In SAT, gene expression of CD14 and LBP correlated significantly to BMI (p≤ 0.001, both), and CD14 and TLR2 expressions were significantly higher in patients with T2DM and MetS compared to patients without (p≤ 0.001, both). Circulating and genetically expressed CD14 associated with use of n-3 PUFAs (p=0.008 and p=0.003, respectively). No other significant associations were found between the measured markers and dietary habits. Conclusion: In patients with established CAD, circulating levels of LBP and gene expression of CD14 and TLR2 in SAT were related to obesity, MetS, T2DM, and hypertension. This suggests that the LPS–LBP–CD14 inflammatory axis is activated in the chronic low-grade inflammation associated with cardiometabolic abnormalities, whereas no significant associations with dietary habits were observed. [ABSTRACT FROM AUTHOR]- Published
- 2024
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4. Gut related inflammation and cardiorespiratory fitness in patients with CAD and type 2 diabetes: a sub-study of a randomized controlled trial on exercise training
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Aune, Susanne Kristine, Byrkjeland, Rune, Solheim, Svein, Arnesen, Harald, Trøseid, Marius, Awoyemi, Ayodeji, Seljeflot, Ingebjørg, and Helseth, Ragnhild
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- 2021
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5. Double-Stranded DNA and NETs Components in Relation to Clinical Outcome After ST-Elevation Myocardial Infarction
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Langseth, Miriam Sjåstad, Helseth, Ragnhild, Ritschel, Vibeke, Hansen, Charlotte Holst, Andersen, Geir Øystein, Eritsland, Jan, Halvorsen, Sigrun, Fagerland, Morten Wang, Solheim, Svein, Arnesen, Harald, Seljeflot, Ingebjørg, and Opstad, Trine Baur
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- 2020
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6. Glucose associated NETosis in patients with ST-elevation myocardial infarction: an observational study
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Helseth, Ragnhild, Knudsen, Eva Cecilie, Eritsland, Jan, Opstad, Trine Baur, Arnesen, Harald, Andersen, Geir Øystein, and Seljeflot, Ingebjørg
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- 2019
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7. Managing patients with prediabetes and type 2 diabetes after coronary events: individual tailoring needed - a cross-sectional study
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Munkhaugen, John, Hjelmesæth, Jøran, Otterstad, Jan Erik, Helseth, Ragnhild, Sollid, Stina Therese, Gjertsen, Erik, Gullestad, Lars, Perk, Joep, Moum, Torbjørn, Husebye, Einar, and Dammen, Toril
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- 2018
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8. The NLRP3 Genetic Variant (rs10754555) Reduces the Risk of Adverse Outcome in Middle-Aged Patients with Chronic Coronary Syndrome.
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Opstad, Trine B., Nordeng, Jostein, Pettersen, Alf-Aage R., Åkra, Sissel, Bratseth, Vibeke, Zaidi, Hani, Helseth, Ragnhild, Solheim, Svein, and Seljeflot, Ingebjørg
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NLRP3 protein ,GENETIC variation ,SINGLE nucleotide polymorphisms ,GENE expression ,ANGINA pectoris - Abstract
Background. Inflammation is central in development of cardiovascular disease (CVD). Aberrant function of the Nod-Like Receptor Protein 3 (NLRP3) inflammasome, a central mediator in the proinflammatory response, has been associated with atherosclerosis. The influence of genetic determinants on this inflammatory pathway and its downstream effects is less known. We aimed to investigate the frequency of a single NLRP3 gene variant according to clinical outcome in CVD and its influence on NLRP3-related markers. Methods. In this observational study, we included 1001 patients with chronic coronary syndrome. Blood samples were drawn at inclusion, including whole-blood and PAXgene tubes for DNA and RNA isolation, respectively. Allelic discrimination of the NLRP3 single nucleotide polymorphism rs10754555 was performed; and gene expression of NLRP3, Toll-Like Receptor 4, Interleukin- (IL-) 1β, and IL-18 was relatively quantified, both methods by RT-PCR. Circulating IL-6, high-sensitivity (hs) C-reactive protein, IL-18, and IL-12 were measured by enzyme-like immunosorbent assays. Clinical endpoints during 2 years (n = 106) were a composite of unstable angina pectoris, myocardial infarction, nonhemorrhagic stroke, and death. Results. Minor allele frequency of the NLRP3 variant was 0.36. In all, no association of the NLRP3 variant with clinical subgroups or outcome was found, neither any significant influence on the genes' mRNA expression or circulating protein. However, in subjects < 56 years (25 percentile), the variant G-allele is associated with significant lower risk of suffering a composite event (OR = 0.43 (95% CI 0.19, 0.97), p = 0.043 , adjusted). In the same age group, the NLRP3 gene was accordingly downregulated in G-allele carriers vs. noncarriers, and circulating IL12 was significantly reduced (p < 0.05 , both). In subjects > 56 years, no significant effect of the variant was observed. Conclusion. The age-related reduced risk of composite endpoint in rs10754555 G-allele carriers accompanied by diminished NLRP3 mRNA expression is hypothesis generating and needs to be further explored. The study is registered at http://www.clinicaltrials.gov, with identification number NCT00222261. [ABSTRACT FROM AUTHOR]
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- 2022
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9. Gut Leakage and Cardiac Biomarkers after Prolonged Strenuous Exercise.
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AUNE, SUSANNE KRISTINE, BONNEVIE-SVENDSEN, MARTIN, NYBORG, CHRISTOFFER, TRØSEID, MARIUS, SELJEFLOT, INGEBJØRG, HISDAL, JONNY, and HELSETH, RAGNHILD
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- 2022
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10. Circulating Microvesicles in Association with the NLRP3 Inflammasome in Coronary Thrombi from STEMI Patients.
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Bratseth, Vibeke, Nordeng, Jostein, Helseth, Ragnhild, Solheim, Svein, Åkra, Sissel, Arnesen, Harald, Chiva-Blanch, Gemma, and Seljeflot, Ingebjørg
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NLRP3 protein ,INFLAMMASOMES ,ST elevation myocardial infarction ,EXTRACELLULAR vesicles ,MYOCARDIAL injury - Abstract
Microvesicles (MVs) are actively secreted by cells. The NLRP3-inflammasome and the interleukin 6 (IL-6)-pathways are central in cardiovascular disease. Knowledge of how the inflammasome influences the MVs is limited. In a cross-sectional study, we assessed whether MVs in plasma associate with genes encoding inflammasome signalling in coronary thrombi. Moreover, any relationships between inflammasome activation and phosphatidylserine (PS) externalization, determined through Annexin V (AV
+ ) labelling, and myocardial injury, assessed by cardiac troponin T (cTnT), were analysed. Intracoronary thrombi and blood samples from STEMI patients (n = 33) were investigated. mRNA of NLRP3, caspase-1, interleukin-1β (IL-1β), interleukin-18 (IL-18), IL-6, soluble IL-6-receptor (sIL-6R), and glycoprotein-130 (gp130) were isolated from the thrombi and relatively quantified by RT-PCR. MVs were analysed by flow cytometry. Total AV+ MVs, mainly reflecting hypercoagulability, correlated positively to NLRP3 gene expression (r = 0.545, p = 0.009). A similar pattern was seen for platelet, endothelial and leukocyte derived MVs, separately. The majority of the MVs were AV− (96%). Total and AV− MVs correlated inversely with IL-1β (r = −0.399 and −0.438, respectively, p < 0.05, both) and gp130 (r = −0.457 and −0.502, respectively, p < 0.05, both). No correlations between MVs and cTnT were observed. Our findings indicate an association between NLRP3-inflammasome in coronary thrombi and procoagulant AV+ MVs in STEMI patients. The inverse relationships between AV− MVs and the gene expression of inflammasome activation may indicate an immuno-dampening role of this subpopulation. [ABSTRACT FROM AUTHOR]- Published
- 2022
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11. TIMP-1 expression in coronary thrombi associate with myocardial injury in ST-elevation myocardial infarction patients.
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Nordeng, Jostein, Schandiz, Hossein, Solheim, Svein, Åkra, Sissel, Hoffman, Pavel, Roald, Borghild, Bendz, Bjørn, Arnesen, Harald, Helseth, Ragnhild, and Seljeflot, Ingebjørg
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- 2022
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12. NEUTROPHIL EXTRACELLULAR TRAPS ARE INVERSELY RELATED TO MYOCARDIAL SALVAGE IN ST-ELEVATION MYOCARDIAL INFARCTION INDEPENDENT OF TOCILIZUMAB TREATMENT
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Kindberg, Kristine Mork, Broch, Kaspar, Andersen, Geir, Anstensrud, Anne Kristine, Aakra, Sissel, Woxholt, Sindre, Opdahl, Anders, Wiseth, Rune, Gullestad, Lars, Aukrust, Pal, Seljeflot, Ingebjorg, and Helseth, Ragnhild
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- 2023
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13. NETosis in Long-Term Type 1 Diabetes Mellitus and Its Link to Coronary Artery Disease.
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Aukrust, Sverre Grøver, Holte, Kristine Bech, Opstad, Trine B., Seljeflot, Ingebjørg, Berg, Tore Julsrud, and Helseth, Ragnhild
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TYPE 1 diabetes ,CORONARY artery disease ,CORONARY artery stenosis ,CORONARY disease ,DNA - Abstract
Background: Neutrophil extracellular traps NETs have been linked to glucose and the pathogenesis of type 1 diabetes mellitus (T1DM). NETs also play a role in vascular inflammation and the development of coronary artery disease (CAD). The role of NETs in CAD progression in patients with long-term T1DM is unclear. We aimed to 1) investigate whether levels of circulating NETs markers were elevated in long-term T1DM subjects compared to controls, and 2) explore whether levels of NETs were related to the presence of CAD. Material and Methods: 102 patients with > 45 years of T1DM and 75 age-matched controls were enrolled in a cross-sectional study. Median age was 62 years. Computed tomography coronary angiography (CTCA) was performed in 148 subjects without established coronary heart disease. For the current study, CAD was defined as a coronary artery stenosis >50%. Double-stranded deoxyribonucleic acid (dsDNA) was measured by a nucleic acid stain, myeloperoxidase-DNA (MPO-DNA), citrullinated histone 3 (H3Cit) and peptidylarginine deiminase 4 (PAD4) by ELISAs, while gene expression of PAD4 was measured in leukocytes from PAXgene tubes. Results: Circulating MPO-DNA levels were significantly lower in patients with T1DM than in controls (0.17 vs 0.29 OD, p<0.001), while dsDNA, H3Cit, PAD4 and gene expression of PAD4 did not differ with respect to the presence of T1DM. There were no significant associations between NETs markers and HbA1c in the T1DM group. None of the NETs markers differed according to the presence of CAD in patients with T1DM. While all circulating NETs markers correlated significantly with circulating neutrophils in the control group (r=0.292-393, p<0.014), only H3Cit and PAD4 correlated with neutrophils in the T1DM group (r= 0.330-0.449, p ≤ 0.001). Conclusions: In this cross-sectional study of patients with long-term T1DM and age-matched controls, circulating NETs levels were not consistently associated with the presence of T1DM or glycemic status, and did not differ according to the presence of CAD in patients with T1DM. Our results entail the possibility of altered neutrophil function and reduced NETosis in T1DM. This warrants further investigation. [ABSTRACT FROM AUTHOR]
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- 2022
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14. The Inflammasome Signaling Pathway Is Actively Regulated and Related to Myocardial Damage in Coronary Thrombi from Patients with STEMI.
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Nordeng, Jostein, Schandiz, Hossein, Solheim, Svein, Åkra, Sissel, Hoffman, Pavel, Roald, Borghild, Bendz, Bjørn, Arnesen, Harald, Helseth, Ragnhild, and Seljeflot, Ingebjørg
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INFLAMMASOMES ,NLRP3 protein ,HISTOLOGY ,REPERFUSION injury ,TROPONIN ,MYOCARDIAL reperfusion ,MYOCARDIAL infarction - Abstract
Background. The Nod-Like-Receptor-Protein-3 (NLRP3) inflammasome and the Interleukin-6 (IL-6) pathways are central mechanisms of the inflammatory response in myocardial reperfusion injury. Expanding our knowledge about the inflammasome signaling axis is important to improve treatment options. In a cross-sectional study, we aimed to study presence, localization, and genetic expression of inflammasome- and IL-6- signaling-related proteins in coronary thrombi and circulating leukocytes from ST-elevation myocardial infarction (STEMI) patients, with relation to myocardial injury and time from symptoms to PCI. Methods. Intracoronary thrombi were aspirated from 33 STEMI patients. Blood samples were drawn. mRNA of Toll-Like-Receptor-4 (TLR4), NLRP3, caspase 1, Interleukin-1β (IL1-β), Interleukin-18 (IL-18), IL-6, IL-6-receptor (IL-6R), and glycoprotein 130 (gp130) were isolated from thrombi and circulating leukocytes and relatively quantified by RT-PCR. A part of each thrombus was embedded in paraffin for histology and immunohistochemistry analyses. Results. Genes encoding the 8 markers were present in 76-100% of thrombi. Expression of TLR4 in thrombi significantly correlated to troponin T (r = 0.455 , p = 0.013), as did NLRP3 (r = 0.468 , p = 0.024). Troponin T correlated with expression in circulating leukocytes of TLR4 (r = 0.438 , p = 0.011), NLRP3 (r = 0.420 , p = 0.0149), and IL-1β (r = 0.394 , p = 0.023). IL-6R expression in thrombi correlated significantly to troponin T (r = 0.434 , p = 0.019), whereas gp130 was inversely correlated (r = − 0.398 , p = 0.050). IL-6 in circulating leukocytes correlated inversely to troponin T (r = − 0.421 , p = 0.015). There were no significant correlations between genes expressed in thrombi and time from symptom to PCI. Conclusions. The inflammasome signaling pathway was actively regulated in coronary thrombi and in circulating leukocytes from patients with STEMI, in association with myocardial damage measured by troponin T. This supports the strategy of medically targeting this pathway in treating myocardial infarction and contributes to sort out optimal timing and targets for anti-inflammatory treatment. The study is registered at clinicaltrials.gov with identification number NCT02746822. [ABSTRACT FROM AUTHOR]
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- 2021
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15. Impact of Preinjury Antithrombotic Therapy on 30–Day Mortality in Older Patients Hospitalized With Traumatic Brain Injury (TBI).
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Rønning, Pål, Helseth, Eirik, Skaansar, Ola, Tverdal, Cathrine, Andelic, Nada, Bhatnagar, Rahul, Melberg, Mathias, Skaga, Nils Oddvar, Aarhus, Mads, Halvorsen, Sigrun, and Helseth, Ragnhild
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FIBRINOLYTIC agents ,OLDER patients ,BRAIN injuries ,COMPUTED tomography ,LOGISTIC regression analysis - Abstract
Objective: Elderly patients are frequently in need of antithrombotic therapy for reducing thrombotic events. The association between antithrombotic drugs and survival after traumatic brain injury (TBI) is, nevertheless, unclear. Methods: This retrospective study included patients ≥65 years admitted to a Norwegian Level 1 trauma center with TBI identified on cerebral computed tomography (cerebral-CT) during 2014–2019. Preinjury use of antiplatelets and anticoagulants was compared to the prescription rate in the general Norwegian population. The primary outcome was 30-day mortality. Uni- and multivariate logistic regression analyses estimated the association between the use of antithrombotic drugs and mortality. Results: The study includes 832 consecutive TBI patients ≥65 years. The median age was 76 years, 58% were males, 51% had moderate or severe TBI, and 39% had multiple traumas. Preinjury use of antithrombotics was registered in 471/832 (55.6%) patients; antiplatelet therapy alone in 268, anticoagulant therapy alone in 172, and combined antiplatelet and anticoagulant therapy in 31. Antiplatelet use did not differ between the study cohort and the general Norwegian population ≥65 years (31 vs. 31%, p = 0.87). Anticoagulant therapy was used more commonly in the study cohort than in the general Norwegian population (24 vs. 19%, p = 0.04). Combined use of antiplatelet and anticoagulant therapy was significantly associated with 30-day mortality, while preinjury antiplatelet or anticoagulation treatment alone was not. No difference in 30-day mortality between patients using VKA, DOACs, or LMWH was encountered. Conclusions: In this cohort, neither antiplatelet nor anticoagulant therapy alone was associated with increased 30-day mortality. Anticoagulant use was more prevalent among TBI patients than the general population, suggesting that anticoagulation might contribute to the initiation of intracranial bleeding after blunt head trauma. Combined antiplatelet and anticoagulant therapy posed increased risk of 30-day mortality. [ABSTRACT FROM AUTHOR]
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- 2021
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16. Tocilizumab increases citrullinated histone 3 in non-ST segment elevation myocardial infarction.
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Helseth, Ragnhild, Kleveland, Ola, Ueland, Thor, Wiseth, Rune, Damas, Jan Kristian, Broch, Kaspar, Michelsen, Annika, Bendz, Bjørn, Gullestad, Lars, Aukrust, Pål, and Seljeflot, Ingebjørg
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- 2021
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17. Neutrophil extracellular trap components and myocardial recovery in post-ischemic acute heart failure.
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Langseth, Miriam Sjåstad, Andersen, Geir Øystein, Husebye, Trygve, Arnesen, Harald, Zucknick, Manuela, Solheim, Svein, Eritsland, Jan, Seljeflot, Ingebjørg, Opstad, Trine Baur, and Helseth, Ragnhild
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Objective: The role of neutrophil extracellular traps (NETs) in acute heart failure is unknown. We recently showed that interleukin 8, a putative NETs stimulator, was associated with myocardial recovery in acute heart failure complicating ST-elevation myocardial infarction (STEMI). In this exploratory post-hoc study, we aimed to investigate the role of NETs components in relation to myocardial function and interleukin 8 in STEMI patients with symptomatic acute heart failure. Methods: In 61 STEMI patients developing acute heart failure within 48 hours of successful revascularization, wall motion score index (WMSI), global longitudinal strain (GLS) and left ventricular ejection fraction (LVEF) were assessed by echocardiography at baseline and on day 5. Blood drawn at baseline and days 1, 2 and 5 was used to quantify double-stranded DNA (dsDNA), myeloperoxidase-DNA complexes (MPO-DNA) and citrullinated histone 3 (CitH3). The area under the curve (AUC) of each NETs marker and interleukin 8 was approximated for the first 5 days. Results: dsDNA
AUC and MPO-DNAAUC correlated significantly with change in WMSI from baseline to day 5 (rs = 0.28 for both, p≤0.05), whereas NETs AUCs did not correlate with changes in GLS and LVEF. dsDNAAUC was significantly correlated with interleukin 8AUC (r = 0.40, p = 0.003). However, mixed model regression could not identify a significant effect of the NETs components on myocardial function parameters. Conclusions: In this cohort with acute heart failure complicating STEMI, NETs components were partly correlated with myocardial function and interleukin 8 levels, yet no causal relationship between NETs components and myocardial recovery could be established. Clinical trial registration: ClinicalTrials.gov, identifier: NCT00324766. [ABSTRACT FROM AUTHOR]- Published
- 2020
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18. Complement Activation in Association with Markers of Neutrophil Extracellular Traps and Acute Myocardial Infarction in Stable Coronary Artery Disease.
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Kluge, Karsten E., Langseth, Miriam S., Opstad, Trine B., Pettersen, Alf Å., Arnesen, Harald, Tønnessen, Theis, Seljeflot, Ingebjørg, and Helseth, Ragnhild
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COMPLEMENT activation ,CORONARY disease ,MYOCARDIAL infarction ,ANGINA pectoris ,ATHEROSCLEROTIC plaque - Abstract
Complement activation and neutrophil extracellular traps (NETs) have both been suggested to drive atherosclerotic plaque progression. Although experimental studies suggest interplay between these two innate immunity components, the relevance in patients with coronary artery disease (CAD) is unclear. The aim of this study was to assess associations between complement activation and NETs in patients with stable CAD and examine the role of complement activation on clinical outcome. Blood samples from a cohort of patients with angiographically verified stable CAD (n = 1001) were analyzed by ELISA for the terminal complement complex (TCC) and by relative quantification for gene expression of the C5a receptor 1 (C5aR1) as markers of complement activation. As markers of NETs, dsDNA was analyzed by fluorescent nucleic acid stain and myeloperoxidase-DNA (MPO-DNA) by ELISA. Clinical outcome was defined as unstable angina, nonhemorrhagic stroke, acute myocardial infarction (MI), or death (n = 106 , whereof 36 MI). Levels of TCC and C5aR1 were not significantly correlated to dsDNA (TCC: r = − 0.045 , p = 0.153 ; C5aR1: r = − 0.060 , p = 0.434) or MPO-DNA (TCC: r = 0.026 , p = 0.414 ; C5aR1: r = 0.123 , p = 0.107). When dividing TCC and C5aR1 levels into quartiles (Q), levels of MPO-DNA differed significantly across quartiles (TCC: p = 0.008 , C5aR1: 0.049), while dsDNA did not (TCC: p = 0.181 , C5aR1: p = 0.771). Patients with TCC levels in Q4 had significantly higher levels of MPO-DNA than Q1-3 (p = 0.019), and C5aR1 levels in Q3-4 had significantly higher levels of MPO-DNA than Q1-2 (p = 0.046). TCC levels did not differ between patients experiencing a clinical endpoint or not, but high levels were associated with increased risk of acute MI (OR. 1.97, 95% CI: 0.99-3.90, p = 0.053) during two-year follow up, also when adjusted for relevant covariates. In conclusion, TCC and C5aR1 were moderately associated with the NET marker MPO-DNA, and TCC levels were related to the risk of future MI in this cohort of patients with stable CAD. [ABSTRACT FROM AUTHOR]
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- 2020
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19. Neutrophil Extracellular Trap Components Associate with Infarct Size, Ventricular Function, and Clinical Outcome in STEMI.
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Helseth, Ragnhild, Shetelig, Christian, Andersen, Geir Øystein, Langseth, Miriam Sjåstad, Limalanathan, Shanmuganathan, Opstad, Trine B., Arnesen, Harald, Hoffmann, Pavel, Eritsland, Jan, and Seljeflot, Ingebjørg
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CARDIAC magnetic resonance imaging , *MEDICAL research ethics , *DNA , *MEDICAL ethics committees , *MYOCARDIAL infarction - Abstract
Background. The relevance of neutrophil extracellular traps (NETs) in acute ST-elevation myocardial infarction (STEMI) is unclear. We explored the temporal profile of circulating NET markers and their associations to myocardial injury and function and to adverse clinical events in STEMI patients. Methods and Results. In 259 patients, blood samples were drawn before and after PCI, on day 1, and after 4 months. Double-stranded deoxyribonucleic acid (dsDNA) and myeloperoxidase-DNA (MPO-DNA) were measured in serum by a nucleic acid stain and ELISA. Cardiac magnetic resonance imaging assessed microvascular obstruction (MVO), area at risk, infarct size, myocardial salvage index, left ventricular ejection fraction (LVEF), and change in indexed left ventricular end-diastolic volume (LVEDVi). Clinical events were registered after 12 months. dsDNA and MPO-DNA levels were highest before PCI, with reduced levels thereafter (all p≤0.02). Patients with high vs. low day 1 dsDNA levels (>median; 366 ng/ml) more frequently had MVO, larger area at risk, larger infarct size acutely and after 4 months, and lower myocardial salvage index (all p<0.03). Moreover, they had lower LVEF acutely and after 4 months, and larger change in LVEDVi (all p≤0.014). High day 1 dsDNA levels also associated with risk of having a large infarct size (>75th percentile) and low LVEF (≤49%) after 4 months when adjusted for gender, time from symptoms to PCI, and infarct localization (OR 2.3 and 3.0, both p<0.021), and patients with high day 1 dsDNA levels were more likely to experience an adverse clinical event, also when adjusting for peak troponin T (hazard ratio 5.1, p=0.012). No such observations were encountered for MPO-DNA. Conclusions. High day 1 dsDNA levels after STEMI were associated with myocardial infarct size, adverse left ventricular remodeling, and clinical outcome. Although the origin of dsDNA could be discussed, these observations indicate a potential role for dsDNA in acute myocardial ischemia. This trial is registered with S-08421d, 2008/10614 (Regional Committee for Medical Research Ethics in South-East Norway (2008)). [ABSTRACT FROM AUTHOR]
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- 2019
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20. Markers of neutrophil extracellular traps are associated with adverse clinical outcome in stable coronary artery disease.
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Langseth, Miriam Sjåstad, Opstad, Trine Baur, Bratseth, Vibeke, Solheim, Svein, Arnesen, Harald, Pettersen, Alf Åge, Seljeflot, Ingebjørg, and Helseth, Ragnhild
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- 2018
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21. The Time Course of Markers of Neutrophil Extracellular Traps in Patients Undergoing Revascularisation for Acute Myocardial Infarction or Stable Angina Pectoris.
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Helseth, Ragnhild, Solheim, Svein, Arnesen, Harald, Seljeflot, Ingebjørg, and Opstad, Trine Baur
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TROPONIN , *THROMBOSIS , *MYOCARDIAL infarction complications , *CORONARY circulation , *KINASES - Abstract
Background and Aims. Neutrophil extracellular traps (NETs) have been identified in acute myocardial infarction. We assessed the time profile and association with infarct size for NETs markers in ST-elevation myocardial infarction (STEMI) and stable angina pectoris (AP). Methods. In 20 patients with STEMI and 10 with AP undergoing percutaneous coronary intervention (PCI), blood samples were collected before PCI (only AP group) and after 3 and 12 hours, days 1, 3, 5, 7, and 14 for measurement of NETs markers. Results. Double-stranded deoxyribonucleic acid (dsDNA) and nucleosome levels were higher in STEMI than AP until day 3 and 12 hours (p<0.03, all). DsDNA declined after day 5 in both groups (p<0.04, all), while nucleosomes declined until day 3 only in the AP group (p<0.05, all). DsDNA correlated with peak troponin T and creatine kinase MB (CKMB) at day 5 (r=0.48, p=0.03, both) and with MRI-measured infarct size at days 5 and 7 (r=0.61, p=0.01 and r=0.52, p=0.04, resp.), while nucleosomes correlated with infarct size at day 5 (r=0.58, p=0.02). Conclusions. High levels of NETs markers were observed in STEMI shortly after revascularisation and were partly associated with infarct size. The decline thereafter in both groups indicates a role for NETs in both acute and chronic atherothrombosis. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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22. Associations between circulating proteins and corresponding genes expressed in coronary thrombi in patients with acute myocardial infarction.
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Helseth, Ragnhild, Weiss, Thomas W., Opstad, Trine Baur, Siegbahn, Agneta, Solheim, Svein, Freynhofer, Matthias K., Huber, Kurt, Arnesen, Harald, and Seljeflot, Seljeflot
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PROTEIN analysis , *GENE expression , *THROMBOEMBOLISM , *MYOCARDIAL infarction , *BIOMARKERS , *PATIENTS - Abstract
Introduction Several genes are expressed in aspirated coronary thrombi in acute myocardial infarction (AMI), exhibiting dynamic changes along ischemic time. Whether soluble biomarkers reflect the local gene environment and ischemic time is unclear. We explored whether circulating biomarkers were associated with corresponding coronary thrombi genes and total ischemic time. Material and methods In 33 AMI patients undergoing percutaneous coronary intervention (PCI), blood samples were collected within 6–24 h for markers related to plaque rupture (metalloproteinase 9, tissue inhibitor of metalloproteinases 1), platelet and endothelial cell activation (P-selectin, CD40 ligand, PAR-1), hemostasis (tissue factor, tissue plasminogen activator, plasminogen activator inhibitor 1, free and total tissue factor pathway inhibitor, D-dimer, prothrombin fragment 1 + 2), inflammation (interleukin 8 and 18, fractalkine, monocyte chemoattractant protein 1 (MCP-1), CXCL1, pentraxin 3, myeloperoxidase) and galectin 3, caspase 8 and epidermal growth factor (EGF). Laboratory analyses were performed by Proximity Extension Assay (Proseek Multiplex CVD I 96 × 96 ), ELISAs and RT-PCR. Results Only circulating P-selectin correlated to the corresponding P-selectin gene expression in thrombi (r = 0.530, p = 0.002). Plasma galectin 3, fractalkine, MCP-1 and caspase 8 correlated inversely to ischemic time (r = − 0.38–0.50, all p < 0.05), while plasma MCP-1, galectin 3 and EGF were higher at short (≤ 4 h) vs. long (> 4 h) ischemic time (all p < 0.05). Conclusions The dynamic changes in circulating mediators along ischemic time were not reflected in the profile of locally expressed genes. These observations indicate a locally confined milieu within the site of atherothrombosis, which may be important for selective therapy. [ABSTRACT FROM AUTHOR]
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- 2015
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23. Gestational diabetes mellitus among Nordic Caucasian women: Prevalence and risk factors according to WHO and simplified IADPSG criteria.
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Helseth, Ragnhild, Salvesen, Øyvind, Stafne, Signe N., Mørkved, Siv, Salvesen, Kjell A., and Carlsen, Sven M.
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GESTATIONAL diabetes , *PREGNANCY complications , *DISEASES in women , *DIAGNOSIS - Abstract
Background. Gestational diabetes mellitus (GDM) is associated with both maternal and offspring adverse effects. The World Health Organization (WHO) has recently adopted novel GDM criteria. The aim of this study was to evaluate the former WHO and a simplified version of the new International Association for Diabetes in Pregnancy Study Group (IADPSG) criteria as to prevalence of and risk factors for GDM in a Nordic Caucasian population. Methods. A 75 g oral glucose tolerance test was performed in 687 women at 18-22 and 32-36 pregnancy weeks. GDM was defined according to the WHO criteria as fasting plasma glucose ≥ 7.0 mmol/L and/or 2-hour plasma glucose ≥ 7.8 mmol/L and by a simplified version of the IADPSG criteria as either fasting glucose ≥ 5.1 mmol/L and/or 2-h plasma glucose ≥ 8.5 mmol/L. One-hour glucose values were not available and were thus not included in the diagnosis of GDM by IADPSG. Prevalence of GDM during pregnancy and risk factors for GDM at 18-22 weeks were studied in retrospect according to each of the two criteria. Results. The total prevalence of GDM during pregnancy was 6.1% (42/687) for the WHO criteria and 7.4% (51/687) for the simplified IADPSG criteria. High maternal age and short stature were independently associated with WHO GDM. Maternal age, fasting insulin and no regular exercise at 18-22 pregnancy weeks associated with simplified IADPSG GDM. Conclusions. Simplified IADPSG criteria moderately increase GDM prevalence compared with the WHO criteria. Risk factors for GDM differ with the diagnostic criteria used. [ABSTRACT FROM AUTHOR]
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- 2014
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24. Maternal and fetal insulin levels at birth in women with polycystic ovary syndrome: data from a randomized controlled study on metformin.
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Helseth, Ragnhild, Vanky, Eszter, Stridsklev, Solhild, Vogt, Christina, and Carlsen, Sven M.
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METFORMIN , *POLYCYSTIC ovary syndrome , *INSULIN , *RANDOMIZED controlled trials , *HEALTH outcome assessment , *UMBILICAL cord , *PLACENTA , *FETUS - Abstract
Context: Metformin is suggested to reduce pregnancy complications in women with polycystic ovary syndrome (PCOS). Metformin crosses the placenta and therapeutic concentrations are measured in the fetal circulation. Whether metformin treatment in pregnant PCOS women affects maternal and fetal insulin concentrations at birth is not clarified. Objectives: To investigate the possible effect of metformin on insulin concentrations in umbilical cord blood and the possible association between maternal and fetal insulin concentrations. Design: Post-hoc analysis of a subgroup of PCOS women participating in a double-blind randomized controlled trial. Setting: University hospital setting. Participants: Women with PCOS (n=118), aged 19-39 years. Main outcome measures: Maternal and umbilical cord insulin concentrations immediately after birth. Results: At delivery women randomized to metformin had lower insulin concentrations than those randomized to placebo (259±209 vs 361±261 pmol/l; P=0.020). No difference was found in insulin concentrations in umbilical venous (P=0.95) and arterial (P=0.39) blood between the metformin and placebo groups. The arteriovenous difference was also equal between the groups (P=0.38). Insulin concentrations were higher in the umbilical vein than in the umbilical artery independent of randomization (70±51 vs 45±48 pmol/l; P<0.0005). Conclusions: In PCOS, metformin treatment during pregnancy resulted in lower maternal insulin concentrations at delivery. Metformin treatment did not affect fetal insulin concentrations. Higher insulin concentrations in the umbilical vein indicate that the placenta somehow secretes insulin to the fetus. The possibility of placental insulin secretion to the fetus deserves further investigations. [ABSTRACT FROM AUTHOR]
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- 2014
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25. Androgens and hyperemesis gravidarum: a case-control study.
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Helseth, Ragnhild, Ravlo, Merethe, Carlsen, Sven M, and Eszter Vanky, E
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- 2014
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26. The Time Profile of Pentraxin 3 in Patients with Acute ST-Elevation Myocardial Infarction and Stable Angina Pectoris Undergoing Percutaneous Coronary Intervention.
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Helseth, Ragnhild, Solheim, Svein, Opstad, Trine, Hoffmann, Pavel, Arnesen, Harald, and Seljeflot, Ingebjørg
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PENTRAXINS , *MYOCARDIAL infarction , *ANGINA pectoris , *ANGIOPLASTY , *GENE expression , *BLOOD sampling - Abstract
Background. High levels of Pentraxin 3 (PTX3) are reported in acute myocardial infarction (AMI). Aim. To investigate circulating levels and gene expression of PTX3 in patients with AMI and stable angina pectoris (AP) undergoing PCI. Methods. Ten patients with AP and 20 patients with AMI were included. Blood samples were drawn before PCI in the AP group and after 3 and 12 hours and days 1, 3, 5, 7, and 14 in both groups. Results. Circulating PTX3 levels were higher in AMI compared to AP at 3 and 12 hours (P < 0.001 and P = 0.003). Within the AMI group, reduction from 3 hours to all later time points was observed (all P ⩽ 0.001). Within the AP group, increase frombaseline to 3 hours (P = 0.022), followed by reductions thereafter (all P < 0.05), was observed. PTX3 mRNA increased in the AMI group from 3 hours to days 7 and 14 in a relative manner of 62% and 73%, while a relative reduction from baseline to 3 and 12 hours of 29% and 37% was seen in the AP group. Conclusion. High circulating PTX3 levels shortly after PCI in AMI indicate that AMI itself influences PTX3 levels. PTX3 mRNA might be in response to fluctuations in circulating levels. [ABSTRACT FROM AUTHOR]
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- 2014
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27. Gut Leakage Markers in Response to Strenuous Exercise in Patients with Suspected Coronary Artery Disease.
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Aune, Susanne Kristine, Cwikiel, Joanna, Flaa, Arnljot, Arnesen, Harald, Solheim, Svein, Awoyemi, Ayodeji, Trøseid, Marius, Seljeflot, Ingebjørg, and Helseth, Ragnhild
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CORONARY artery disease ,EXERCISE tests ,LIPOPOLYSACCHARIDES ,LEAKAGE ,CORONARY angiography ,CARRIER proteins ,TOLL-like receptors - Abstract
Elevated levels of gut leakage markers have been shown after strenuous exercise in healthy individuals. Any association between a temporary increase in these markers and the presence of coronary artery disease (CAD) is unknown. We therefore aimed to explore circulating gut leakage markers in response to a bout of strenuous exercise in patients with symptoms of CAD. Patients referred to exercise stress testing due to symptoms of CAD were included (n = 287). A maximal exercise ECG stress test was performed and venous blood samples were drawn at rest and within five minutes after, for analysis of soluble cluster of differentiation 14 (sCD14), lipopolysaccharide-binding protein (LBP), intestinal fatty-acid binding protein (I-FABP), lipopolysaccharide (LPS) and gene expression of toll-like receptor 4 (TLR4) in circulating leukocytes. Patients then underwent coronary angiography. LPS, LBP and sCD14 increased significantly after strenuous exercise in patients with symptoms of CAD, suggesting that even short bouts of vigorous exercise are associated with gut leakage. The gene expression of TLR4 decreased significantly after exercise, possibly as a negative feedback to the increase in LPS. There were no differences in exercise-induced changes between the groups of CAD, suggesting gut leakage to be independent of the presence of CAD. [ABSTRACT FROM AUTHOR]
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- 2021
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28. EFFECT OF A SINGLE DOSE OF THE INTERLEUKIN-6 RECEPTOR ANTAGONIST TOCILIZUMAB ON MARKERS OF NEUTROPHIL EXTRACELLULAR TRAPS IN PATIENTS WITH NON-ST ELEVATION MYOCARDIAL INFARCTION.
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Helseth, Ragnhild, Kleveland, Ola, Ueland, Thor, Wiseth, Rune, Damaas, Jan Kristian, Broch, Kaspar, Michelsen, Annika Elisabet, Bendz, Bjørn, Gullestad, Lars, Aukrust, Paal, and Seljeflot, Ingebjoerg
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INTERLEUKIN-6 receptors , *MYOCARDIAL infarction , *TOCILIZUMAB - Published
- 2020
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29. Koronar genekspresjon og leukocyttaktivering.
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Helseth, Ragnhild
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- 2016
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30. Coagulation factors XI and XII as possible targets for anticoagulant therapy.
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Kluge, Karsten Engseth, Seljeflot, Ingebjørg, Arnesen, Harald, Jensen, Torstein, Halvorsen, Sigrun, and Helseth, Ragnhild
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ENOXAPARIN , *BLOOD coagulation factors , *MECHANICAL hearts , *PROSTHETIC heart valves , *VENOUS thrombosis , *FIBRINOLYTIC agents , *TOTAL knee replacement - Abstract
In this review, we give an overview over observational and experimental studies supporting factors XI and XII as targets for anticoagulant therapy. The majority of observational studies on FXI report low concentrations of FXI to be protective against ischemic stroke and venous thrombosis. There is also extensive evidence from experimental and animal studies supporting FXI inhibition as a target for anticoagulant therapy, alone or in combination with other antithrombotic treatments. Four Phase 2 clinical trials on patients undergoing total knee arthroplasty showed non-inferiority or superiority of FXI inhibition compared to enoxaparin for the primary outcome, which was incidence of venous thromboembolism. One Phase 2 trial reported that FXI inhibition is associated with fewer bleeding events than apixaban. The results from observational studies on FXII are more conflicting. Some show that low FXII concentrations confer protection against thrombosis, while others have found it to be deleterious. Results from experimental studies are inconclusive, but suggest that FXII inhibition might be useful in preventing thrombosis caused by foreign objects like catheters or mechanical heart valves. One Phase 2 study not conducted on thrombosis has reported FXII inhibition as safe. In conclusion, FXI seems to be a promising target for antithrombotic therapy, both alone and in combination with existing therapies, while the potential of targeting FXII is still unclear. • Coagulation factors XI and XII may be more important for thrombosis than hemostasis. • Low or absent FXI activity might protect against thrombotic disease. • Some clinical studies have reported FXI inhibitors to be promising anticoagulants. • Studies on the relationship between FXII and thrombotic disease are inconclusive. • FXII inhibition might be utilized in thrombosis caused by artificial surfaces. [ABSTRACT FROM AUTHOR]
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- 2022
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31. Circulating levels of the terminal complement complex are associated with hypercoagulability in patients with stable coronary artery disease.
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Kluge, Karsten E., Langseth, Miriam S., Bratseth, Vibeke, Pettersen, Alf Å., Arnesen, Harald, Tønnessen, Theis, Seljeflot, Ingebjørg, and Helseth, Ragnhild
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CORONARY disease , *COMPLEMENT activation , *BLOOD platelet activation , *HEMOSTASIS , *IMMUNITY - Abstract
• Complement and coagulation activation coincide in coronary artery disease (CAD). • In CAD, complement activation coincides with endothelial activation and damage. • In CAD, complement activation does not coincide with platelet activation. • A novel link between immunity and hemostasis in CAD is demonstrated. [ABSTRACT FROM AUTHOR]
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- 2020
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32. Complement activation in association with clinical outcomes in ST-elevation myocardial infarction.
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Kluge KE, Langseth MS, Andersen GØ, Halvorsen S, Opstad TB, Arnesen H, Tønnessen T, Seljeflot I, and Helseth R
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Introduction: The complement system and neutrophil extracellular traps (NETs) might contribute to ischemia-reperfusion injury in ST-elevation myocardial infarction (STEMI). We aimed to estimate associations between complement activation and NETs in STEMI, and their prognostic value on clinical endpoints., Methods: In this cohort study, 864 patients admitted for PCI during STEMI were included. Complement activation was analyzed by the terminal complement complex (TCC), while NETs were analyzed by myeloperoxidase-DNA, citrullinated histone 3 (CitH3) and dsDNA. The composite endpoint was reinfarction, unscheduled revascularization, stroke, hospitalization due to heart failure, or death, and the secondary endpoint was total mortality. The association between TCC and clinical endpoints was assessed by Cox regression and ROC curve analysis., Results: TCC was weakly correlated to dsDNA ( r = 0.127, p < 0.001) and CitH3 ( r = 0.102, p = 0.003). After a median follow-up time of 4.6 years, 184 (21.3 %) patients had reached a clinical endpoint. TCC was not associated with the composite endpoint, but with total mortality (HR: 1.673, 95 % CI: [1.014, 2.761], p = 0.044). The significant association was lost when adjusting for CRP, NT-proBNP, LVEF and time from symptoms to PCI. In ROC curve analysis of total mortality, the AUC for TCC alone was 0.549 (95 % CI: [0.472, 0.625]), AUC for dsDNA alone was 0.653 (95 % CI: [0.579, 0.720]), while AUC for TCC and dsDNA combined was 0.660 (95 % CI: [0.590, 0.730])., Conclusions: In this STEMI cohort, TCC was not associated with the composite endpoint, but somewhat with total mortality. Combining TCC and dsDNA did not increase the prognostic value compared to dsDNA alone., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)
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- 2022
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33. [Not Available].
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Helseth R
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- 2016
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34. The Effect of Intracoronary Stem Cell Injection on Markers of Leukocyte Activation in Acute Myocardial Infarction.
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Helseth R, Opstad T, Solheim S, Lunde K, Arnesen H, and Seljeflot I
- Abstract
Background: Beneficial effects of stem cell treatment during acute myocardial infarction (AMI) have been suggested, but the effects on inflammation are controversial. The neutrophil cell markers pentraxin 3 (PTX3) and myeloperoxidase (MPO) are both reported to be elevated during AMI. We studied the effects of stem cell treatment in ST-elevation myocardial infarction (STEMI) on PTX3 and MPO levels., Methods: Subjects with STEMI undergoing percutaneous coronary intervention (PCI) were randomized to intracoronary injection of bone marrow cells (mBMCs) (n = 50) or controls (n = 50). Blood samples were drawn 1 day before mBMC injection (baseline), after 1 day, 3 days, 2 - 3 weeks and 3 months. Enzyme-linked immunosorbent assay (ELISA) and RT-PCR were used for biochemical analysis. Myocardial necrosis was quantified by single photon emission computed tomography (SPECT) and creatine kinase MB (CKMB) levels., Results: PTX3 and MPO levels did not differ between the groups at any time points. Within the mBMC group, overall changes in both variables were observed (P < 0.01), with decreased levels from baseline throughout. Within the control group, similar patterns were observed. The relative reduction of PTX3 from baseline to day 1 was significantly less pronounced in the mBMC group compared to controls (P = 0.002), whereas no differences in relative changes from baseline were observed for MPO. Plasma and gene expression levels of PTX3 in leukocytes correlated significantly at all time points (r = 0.379 - 0.448, P < 0.01, all). MPO was significantly correlated to baseline left ventricular ejection fraction (LVEF) (r = -0.229, P = 0.025) and peak CKMB (r = 0.200, P = 0.05)., Conclusions: Stem cell treatment had limited effect on plasma levels of PTX3 and MPO. The initially high PTX3 and MPO levels, the genetic regulation of PTX3 and the association between MPO and myocardial injury support the importance of neutrophil cell activation in STEMI.
- Published
- 2015
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