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Calcific aortic valve stenosis (CAVS) is a common age-related disease characterized by active calcification of the leaflets of the aortic valve. How innate immune cells are involved in disease pathogenesis is not clear. In this study we investigate the role of the pattern recognition receptor Toll-like receptor 7 (TLR7) in CAVS, especially in relation to macrophage subtype. Human aortic valves were used for mRNA expression analysis, immunofluorescence staining, or ex vivo tissue assays. Response to TLR7 agonist in primary macrophages and valvular interstitial cells (VICs) were investigated in vitro. In the aortic valve, TLR7 correlated with M2 macrophage markers on mRNA levels. Expression was higher in the calcified part compared with the intermediate and healthy parts. TLR7+ cells were co-stained with M2-type macrophage receptors CD163 and CD206. Ex vivo stimulation of valve tissue with the TLR7 ligand imiquimod significantly increased secretion of IL-10, TNF-α, and GM-CSF. Primary macrophages responded to imiquimod with increased secretion of IL-10 while isolated VICs did not respond. In summary, in human aortic valves TLR7 expression is associated with M2 macrophages markers. Ex vivo tissue challenge with TLR7 ligand led to secretion of immunomodulatory cytokine IL-10. These results connect TLR7 activation in CAVS to reduced inflammation and improved clearance.
Glykeria Karadimou; Oscar Plunde; Sven-Christian Pawelzik; Miguel Carracedo; Per Eriksson; Anders Franco-Cereceda; Gabrielle Paulsson-Berne; Magnus Bäck. TLR7 Expression is Associated with M2 Macrophage Subset in Calcific Aortic Valve Stenosis. Cells 2020, 9, 1710 .
AMA StyleGlykeria Karadimou, Oscar Plunde, Sven-Christian Pawelzik, Miguel Carracedo, Per Eriksson, Anders Franco-Cereceda, Gabrielle Paulsson-Berne, Magnus Bäck. TLR7 Expression is Associated with M2 Macrophage Subset in Calcific Aortic Valve Stenosis. Cells. 2020; 9 (7):1710.
Chicago/Turabian StyleGlykeria Karadimou; Oscar Plunde; Sven-Christian Pawelzik; Miguel Carracedo; Per Eriksson; Anders Franco-Cereceda; Gabrielle Paulsson-Berne; Magnus Bäck. 2020. "TLR7 Expression is Associated with M2 Macrophage Subset in Calcific Aortic Valve Stenosis." Cells 9, no. 7: 1710.
Persistent low-grade inflammation and premature ageing are hallmarks of the uremic phenotype and contribute to impaired health status, reduced quality of life, and premature mortality in chronic kidney disease (CKD). Because there is a huge global burden of disease due to CKD, treatment strategies targeting inflammation and premature ageing in CKD are of particular interest. Several distinct features of the uremic phenotype may represent potential treatment options to attenuate the risk of progression and poor outcome in CKD. The nuclear factor erythroid 2-related factor 2 (NRF2)–kelch-like erythroid cell-derived protein with CNC homology [ECH]-associated protein 1 (KEAP1) signaling pathway, the endocrine phosphate-fibroblast growth factor-23–klotho axis, increased cellular senescence, and impaired mitochondrial biogenesis are currently the most promising candidates, and different pharmaceutical compounds are already under evaluation. If studies in humans show beneficial effects, carefully phenotyped patients with CKD can benefit from them.
Thomas Ebert; Sven-Christian Pawelzik; Anna Witasp; Samsul Arefin; Sam Hobson; Karolina Kublickiene; Paul G. Shiels; Magnus Bäck; Peter Stenvinkel. Inflammation and Premature Ageing in Chronic Kidney Disease. Toxins 2020, 12, 227 .
AMA StyleThomas Ebert, Sven-Christian Pawelzik, Anna Witasp, Samsul Arefin, Sam Hobson, Karolina Kublickiene, Paul G. Shiels, Magnus Bäck, Peter Stenvinkel. Inflammation and Premature Ageing in Chronic Kidney Disease. Toxins. 2020; 12 (4):227.
Chicago/Turabian StyleThomas Ebert; Sven-Christian Pawelzik; Anna Witasp; Samsul Arefin; Sam Hobson; Karolina Kublickiene; Paul G. Shiels; Magnus Bäck; Peter Stenvinkel. 2020. "Inflammation and Premature Ageing in Chronic Kidney Disease." Toxins 12, no. 4: 227.
Eastern Remedies for Western-type diet induced atherosclerosis
Sven-Christian Pawelzik; Magnus Bäck. Eastern Remedies for Western-type diet induced atherosclerosis. Annals of Translational Medicine 2020, 8, 258 -258.
AMA StyleSven-Christian Pawelzik, Magnus Bäck. Eastern Remedies for Western-type diet induced atherosclerosis. Annals of Translational Medicine. 2020; 8 (6):258-258.
Chicago/Turabian StyleSven-Christian Pawelzik; Magnus Bäck. 2020. "Eastern Remedies for Western-type diet induced atherosclerosis." Annals of Translational Medicine 8, no. 6: 258-258.
Obesity is associated with low-grade chronic inflammation, which contributes to the development of the metabolic syndrome and its associated complications, such as insulin resistance and type-2 diabetes. Limited data from animal and human studies support local generation of pro-inflammatory prostanoid lipid mediators in white adipose tissue. However, the link between systemic prostanoid levels and parameters characterizing the metabolic syndrome is missing in human obesity. Therefore, we performed a targeted lipidomic analysis using urine samples from obese human subjects (n = 45) and show for the first time in humans that urinary prostanoid levels correlate with metabolic parameters that indicate a dysregulated glucose and triglyceride metabolism. We identified tetranor-PGDM and tetranor-PGEM as the two major urinary prostanoid metabolites in obese subjects with levels of 247 ± 31 and 23.3 ± 4.0 pmol/mg creatinine, respectively. Tetranor-PGDM was significantly associated with serum triglycerides, while tetranor-PGEM was associated with abdominal obesity as defined by an increased waist-to-hip ratio (WHR), with glycated hemoglobin (HbA1c), and with impaired oral glucose tolerance. These results confirm the previously established notion of low-grade chronic inflammation in obesity and further identify an association of the prostanoid pathway with obesity-associated dyslipidemia, abdominal obesity, and insulin resistance.
Sven-Christian Pawelzik; Antoine Avignon; Helena Idborg; Catherine Boegner; Françoise Stanke-Labesque; Per-Johan Jakobsson; Ariane Sultan; Magnus Bäck. Urinary prostaglandin D2 and E2 metabolites associate with abdominal obesity, glucose metabolism, and triglycerides in obese subjects. Prostaglandins & Other Lipid Mediators 2019, 145, 106361 .
AMA StyleSven-Christian Pawelzik, Antoine Avignon, Helena Idborg, Catherine Boegner, Françoise Stanke-Labesque, Per-Johan Jakobsson, Ariane Sultan, Magnus Bäck. Urinary prostaglandin D2 and E2 metabolites associate with abdominal obesity, glucose metabolism, and triglycerides in obese subjects. Prostaglandins & Other Lipid Mediators. 2019; 145 ():106361.
Chicago/Turabian StyleSven-Christian Pawelzik; Antoine Avignon; Helena Idborg; Catherine Boegner; Françoise Stanke-Labesque; Per-Johan Jakobsson; Ariane Sultan; Magnus Bäck. 2019. "Urinary prostaglandin D2 and E2 metabolites associate with abdominal obesity, glucose metabolism, and triglycerides in obese subjects." Prostaglandins & Other Lipid Mediators 145, no. : 106361.