| 1. |
- Turczynska, Karolina, et al.
(författare)
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Regulation of Smooth Muscle Dystrophin and Synaptopodin 2 Expression by Actin Polymerization and Vascular Injury.
- 2015
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1524-4636. ; 35:6, s. 1489-1497
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Tidskriftsartikel (refereegranskat)abstract
- Actin dynamics in vascular smooth muscle is known to regulate contractile differentiation and may play a role in the pathogenesis of vascular disease. However, the list of genes regulated by actin polymerization in smooth muscle remains incomprehensive. Thus, the objective of this study was to identify actin-regulated genes in smooth muscle and to demonstrate the role of these genes in the regulation of vascular smooth muscle phenotype.
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| 2. |
- Akner, Gunnar, 1953-, et al.
(författare)
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Vi står gärna bakom en utfallsbaserad vård
- 2017
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Ingår i: Dagens Samhälle. - 1652-6511.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Jörgen Nordenström försöker få det till att vår kritik av värdebaserad vård egentligen handlar om att vi vill ha mer resurser. Han har helt missuppfattat oss, skriver 26 specialistläkare i en replik.
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| 3. |
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| 4. |
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| 5. |
- Folkersen, Lasse, et al.
(författare)
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Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.
- 2020
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Ingår i: Nature metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:10, s. 1135-1148
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Tidskriftsartikel (refereegranskat)abstract
- Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.
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| 6. |
- Hien, Tran T., et al.
(författare)
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MicroRNA-dependent regulation of KLF4 by glucose in vascular smooth muscle
- 2018
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Ingår i: Journal of Cellular Physiology. - : Wiley. - 0021-9541 .- 1097-4652. ; 233:9, s. 7195-7205
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Tidskriftsartikel (refereegranskat)abstract
- Diabetes is a major risk factor for cardiovascular disease and this is in part due to the effects of hyperglycemia on vascular smooth muscle cells. Small non-coding microRNAs are known to control smooth muscle phenotype and arterial contractility and are dysregulated in diabetes. The effect of microRNAs on smooth muscle differentiation is in part mediated by the transcription factor KLF4 but the role of this mechanism in diabetic vascular disease is not fully understood. Herein, we have investigated the importance of hyperglycemia and diabetes for the expression of KLF4 in vascular smooth muscle and the involvement of miRNAs in this regulation. Hyperglycemia down-regulated KLF4 in vascular smooth muscle cells and similar results were found in arteries of diabetic mice and patients. This correlated with a Foxa2-dependent up-regulation of miR-29c, which targeted KLF4 in vascular smooth muscle cells. Importantly, by preventing downregulation of KLF4, the induction of smooth muscle contractile protein markers by glucose was inhibited. In conclusion, miR-29 mediated inhibition of KLF4 in hyperglycemic conditions contributes to increased expression of contractile markers in vascular smooth muscle cells. Further studies are warranted to determine the therapeutic implications of miR-29 inhibition in diabetic vascular disease.
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| 7. |
- Hien Tran, Thi, et al.
(författare)
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Elevated glucose levels promote contractile and cytoskeletal gene expression in vascular smooth muscle via Rho/protein kinase C and actin polymerization.
- 2016
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 291:7, s. 68-3552
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Tidskriftsartikel (refereegranskat)abstract
- Both type 1 and type 2 diabetes are associated with increased risk of cardiovascular disease. This is in part attributed to the effects of hyperglycemia on vascular endothelial and smooth muscle cells but the underlying mechanisms are not fully understood. In diabetic animal models, hyperglycemia results in hyper-contractility of vascular smooth muscle possibly due to increased activation of Rho-kinase. The aim of the present study was to investigate the regulation of contractile smooth muscle markers by glucose and to determine the signaling pathways that are activated by hyperglycemia in smooth muscle cells. Microarray, qPCR and western blot analyses revealed that both mRNA and protein expression of contractile smooth muscle markers was increased in isolated smooth muscle cells cultured under high compared to low glucose conditions. This effect was also observed in hyperglycemic Akita mice and in diabetic patients. Elevated glucose activated the protein kinase C and Rho/Rho-kinase signaling pathways and stimulated actin polymerization. Glucose-induced expression of contractile smooth muscle markers in cultured cells could be partially or completely repressed by inhibitors of advanced glycation end products, L-type calcium channels, protein kinase C, Rho-kinase, actin polymerization and myocardin related transcription factors. Furthermore, genetic ablation of the miR-143/145 cluster prevented the effects of glucose on smooth muscle marker expression. In conclusion, these data demonstrate a possible link between hyperglycemia and vascular disease states associated with smooth muscle contractility.
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| 8. |
- Johansson, Malin, et al.
(författare)
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Prediction of 30-day Mortality after Transcatheter Aortic Valve Implantation: A Comparison of Logistic EuroSCORE, STS score, and EuroSCORE II
- 2014
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Ingår i: Journal of Heart Valve Disease. - 0966-8519. ; 23:5, s. 567-574
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Tidskriftsartikel (refereegranskat)abstract
- Background and aim of the study: The logistic EuroSCORE and STS score have been used for the selection of suitable TAVI patients, but their predictive ability is unsatisfactory. The study aim was to evaluate the performance of the EuroSCORE II in predicting 30-day mortality after TAVI in comparison to the logistic EuroSCORE and STS scoring systems. Methods: Between January 2008 and April 2013, a total of 123 consecutive patients underwent TAVI (transapical, n = 85; transfemoral, n = 38) at the authors' institution. Calibration and discriminatory ability was evaluated for three risk scores models (logistic EuroSCORE, STS score, and EuroSCORE II), and compared for the prediction of 30-day mortality using the Hosmer-Lemeshow test for goodness-of-fit and receiver operating characteristics curve analysis. Results: The overall 30-day mortality was 4.1% (5/123). Predicted mortality was 25.0 +/- 15.7% by logistic EuroSCORE, 7.3 +/- 6.9% by STS score, and 7.8 +/- 8.7% by EuroSCORE II. The observed/expected mortality ratio was 0.16 for logistic EuroSCORE, 0.56 for STS score, and 0.52 for EuroSCORE II. The area under the curve was 0.69 (95% CI 0.54-0.84) for the logistic EuroSCORE, 0.60 (95% CI 0.38-0.82) for the STS score, and 0.66 (95% CI 0.46-0.86) for the EuroSCORE II. Conclusion: In the present study, the EuroSCORE II was found to predict 30-day mortality more accurately for the TAVI cohort than did the more established logistic EuroSCORE, and also to compare (at present) on a par with the STS score. However, there were no differences in discriminatory power between the models. It is believed that, in the absence of a more TAVI-oriented risk stratification system, the EuroSCORE II may be a valuable adjunct in the clinical setting.
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| 10. |
- Lindstedt, Sandra, et al.
(författare)
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Lung transplant after 6 months on ECMO support for SARS-CoV-2-induced ARDS complicated by severe antibody-mediated rejection
- 2021
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Ingår i: BMJ Open Respiratory Research. - : BMJ. - 2052-4439. ; 8, s. 1-4
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Tidskriftsartikel (refereegranskat)abstract
- There have been a few reports of successful lung transplantation (LTx) in patients with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS); however, all reports were with rather short follow-up. Here we present a 62-year-old man without prior lung diseases. Following SARS-CoV-2-induced ARDS and 6 months of extracorporeal membrane oxygenation, he underwent LTx. 3 months post-transplantation he developed acute hypoxia requiring emergency intubation. Chest imaging showed acute rejection, and de novo DQ8-DSA was discovered. He was treated with a high dose of corticosteroids and plasmapheresis and was extubated 4 days later, yet the de novo DQ8-DSA remained. After sessions of plasmapheresis and rituximab, the levels of de novo DQ8-DSA remained unchanged. Nine months post-transplantation the patient died of respiratory failure. We herein discuss the decision to transplant, the transplantation itself and the postoperative course with severe antibody-mediated rejection. In addition, we evaluated the histological changes of the explanted lungs and compared these with end-stage idiopathic pulmonary fibrosis tissue, where both similarities and differences are seen. With the current case experience, one might consider close monitoring regarding DSA, and gives further support that LTx should only be considered for very carefully selected patients.
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