Marine n-3 polyunsaturated fatty acids (PUFAs) exert potential anti-inflammatory effects and might improve long-term outcomes after renal transplantation. We assessed associations between plasma ...phospholipid levels of marine n-3 PUFAs and plasma inflammatory biomarkers 10 weeks after renal transplantation.
Cross-sectional single-center study.
A study population of 861 renal transplant recipients transplanted at Oslo University Hospital between 2007 and 2011.
Plasma phospholipid fatty acids were determined by gas chromatography. Marine n-3 PUFA levels were defined as the sum of eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid levels in weight percentage of total plasma phospholipid fatty acids. Plasma inflammatory biomarkers were measured by enzyme immunoassays. We used multivariable linear regression analysis to assess associations between levels of marine n-3 PUFAs and inflammatory biomarkers in plasma.
Plasma marine n-3 PUFA levels were inversely associated with plasma levels of proinflammatory biomarkers soluble tumor necrosis factor receptor 1 (standardized regression coefficient -0.11, P < .001) and interleukin-6 (standardized regression coefficient -0.09, P = .01). In contrast, there was no association between plasma levels of marine n-3 PUFAs and the anti-inflammatory mediator interleukin-10.
In this renal transplant cohort, inverse associations between plasma levels of marine n-3 PUFAs and markers of inflammation were demonstrated.
Vegetation change of the Arctic tundra due to global warming is a well-known process, but the implication for the belowground microbial communities, key in nutrient cycling and decomposition, is ...poorly understood. We characterized the fungal and bacterial abundances in litter and soil layers across 16 warming experimental sites at 12 circumpolar locations. We investigated the relationship between microbial abundances and nitrogen (N) and carbon (C) isotopic signatures, indicating shifts in microbial processes with warming. Microbial abundances were 2–3 orders of magnitude larger in litter than in soil. Local, site-dependent responses of microbial abundances were variable, and no general effect of warming was detected. The only generalizable trend across sites was a dependence between the warming response ratios and C:N ratio in controls, highlighting a legacy of the vegetation on the microbial response to warming. We detected a positive effect of warming on the litter mass and δ
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N, which was linked to bacterial abundance under warmed conditions. This effect was stronger in experimental sites dominated by deciduous shrubs, suggesting an altered bacterial N-cycling with increased temperatures, mediated by the vegetation, and with possible consequences on ecosystem feedbacks to climate change.
Termination of acute inflammation is an active process orchestrated by lipid mediators (LM) derived from polyunsaturated fatty acids, referred to as specialized pro-resolving mediators (SPM). These ...mediators also provide novel therapeutic opportunities for treating inflammatory disease. However, the regulation of these molecules following acute myocardial infarction (MI) remains of interest.
In this prospective observational study we aimed to profile plasma levels of SPMs in ST-elevation MI (STEMI) patients during the first week following MI. Plasma LM concentrations were measured in patients with STEMI (n = 15) at three time points and compared with stable coronary artery disease (CAD; n = 10) and healthy controls (n = 10).
Our main findings were: (i) Immediately after onset of MI and before peak troponin T levels, STEMI patients had markedly increased levels of SPMs as compared with healthy controls and stable CAD patients, with levels of these mediators declining during follow-up. (ii) The increase in SPMs primarily reflected an increase in docosapentaenoic acid- and docosahexaenoic acid-derived protectins. (iii) Several individual protectins were correlated with the rapid increase in neutrophil counts, but not with CRP. (iv) A shift in 5-LOX activity from the leukotriene B4 pathway to the pro-resolving RvTs was observed.
The temporal regulation of SPMs indicates that resolution mechanisms are activated early during STEMI as part of an endogenous mechanism to initiate repair. Thus strategies to boost the activity and/or efficacy of these endogenous mechanisms may represent novel therapeutic opportunities for treatment of patients with MI.
This work was supported by grants from the South-Eastern Norwegian regional health authority, the European Research Council under the European Union's Horizon 2020 research and innovation program, a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society, and the Barts Charity.
The Wingless (Wnt) pathway has been implicated in the pathogenesis of dilated cardiomyopathy (DCM). To explore the role of Wnt modulators Wnt5a and sFRP3 in DCM patients we analyzed the expression of ...Wnt5a and sFRP3 in plasma and myocardium of DCM patients and evaluated their effects on NFAT luciferase activity in neonatal mouse cardiomyocytes. Elevated circulating Wnt5a (n = 102) was associated with increased pulmonary artery pressures, decreased right ventricular function and adverse outcome, with a stronger association in more severely affected patients. A higher Wnt5a/sFRP3 ratio (n = 25) was found in the right ventricle vs. the left ventricle and was correlated with NFAT activation as well as pulmonary artery pressures. Wnt5a induced NFAT activation and sFRP3 release in cardiomyocytes in vitro, while sFRP3 antagonized Wnt5a. Wnt5a is associated with right ventricular dysfunction and adverse outcome in DCM patients and may promote the progression of DCM through NFAT signaling.
Background: Termination of acute inflammation is an active process orchestrated by lipid mediators (LM) derived from polyunsaturated fatty acids, referred to as specialized pro-resolving mediators ...(SPM). These mediators also provide novel therapeutic opportunities for treating inflammatory disease. However, the regulation of these molecules following acute myocardial infarction (MI) remains of interest. Methods: In this prospective observational study we aimed to profile plasma levels of SPMs in ST-elevation MI (STEMI) patients during the first week following MI. Plasma LM concentrations were measured in patients with STEMI (n = 15) at three time points and compared with stable coronary artery disease (CAD; n = 10) and healthy controls (n = 10). Findings: Our main findings were: (i) Immediately after onset of MI and before peak troponin T levels, STEMI patients had markedly increased levels of SPMs as compared with healthy controls and stable CAD patients, with levels of these mediators declining during follow-up. (ii) The increase in SPMs primarily reflected an increase in docosapentaenoic acid- and docosahexaenoic acid-derived protectins. (iii) Several individual protectins were correlated with the rapid increase in neutrophil counts, but not with CRP. (iv) A shift in 5-LOX activity from the leukotriene B4 pathway to the pro-resolving RvTs was observed. Interpretation: The temporal regulation of SPMs indicates that resolution mechanisms are activated early during STEMI as part of an endogenous mechanism to initiate repair. Thus strategies to boost the activity and/or efficacy of these endogenous mechanisms may represent novel therapeutic opportunities for treatment of patients with MI. Fund: This work was supported by grants from the South-Eastern Norwegian regional health authority, the European Research Council under the European Union's Horizon 2020 research and innovation program, a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society, and the Barts Charity. Keywords: Myocardial infarction, Resolution, Inflammation, Specialized pro-resolving mediators, Polyunsaturated fatty acids
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