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- Rykaczewska, U., et al.
(författare)
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Plaque Evaluation by Ultrasound and Transcriptomics Reveals BCLAF1 as a Regulator of Smooth Muscle Cell Lipid Transdifferentiation in Atherosclerosis
- 2022
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Ingår i: Arteriosclerosis Thrombosis and Vascular Biology. - : Ovid Technologies (Wolters Kluwer Health). - 1079-5642 .- 1524-4636. ; 42:5, s. 659-676
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Tidskriftsartikel (refereegranskat)abstract
- Background: Understanding the processes behind carotid plaque instability is necessary to develop methods for identification of patients and lesions with stroke risk. Here, we investigated molecular signatures in human plaques stratified by echogenicity as assessed by duplex ultrasound. Methods: Lesion echogenicity was correlated to microarray gene expression profiles from carotid endarterectomies (n=96). The findings were extended into studies of human and mouse atherosclerotic lesions in situ, followed by functional investigations in vitro in human carotid smooth muscle cells (SMCs). Results: Pathway analyses highlighted muscle differentiation, iron homeostasis, calcification, matrix organization, cell survival balance, and BCLAF1 (BCL2 [B-cell lymphoma 2]-associated transcription factor 1) as the most significant signatures. BCLAF1 was downregulated in echolucent plaques, positively correlated to proliferation and negatively to apoptosis. By immunohistochemistry, BCLAF1 was found in normal medial SMCs. It was repressed early during atherogenesis but reappeared in CD68+ cells in advanced plaques and interacted with BCL2 by proximity ligation assay. In cultured SMCs, BCLAF1 was induced by differentiation factors and mitogens and suppressed by macrophage-conditioned medium. BCLAF1 silencing led to downregulation of BCL2 and SMC markers, reduced proliferation, and increased apoptosis. Transdifferentiation of SMCs by oxLDL (oxidized low-denisty lipoprotein) was accompanied by upregulation of BCLAF1, CD36, and CD68, while oxLDL exposure with BCLAF1 silencing preserved MYH (myosin heavy chain) 11 expression and prevented transdifferentiation. BCLAF1 was associated with expression of cell differentiation, contractility, viability, and inflammatory genes, as well as the scavenger receptors CD36 and CD68. BCLAF1 expression in CD68+/BCL2+ cells of SMC origin was verified in plaques from MYH11 lineage-tracing atherosclerotic mice. Moreover, BCLAF1 downregulation associated with vulnerability parameters and cardiovascular risk in patients with carotid atherosclerosis. Conclusions: Plaque echogenicity correlated with enrichment of distinct molecular pathways and identified BCLAF1, previously not described in atherosclerosis, as the most significant gene. Functionally, BCLAF1 seems necessary for survival and transdifferentiation of SMCs into a macrophage-like phenotype. The role of BCLAF1 in plaque vulnerability should be further evaluated.
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- Amirpour, A, et al.
(författare)
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Is the analogue cognitive test from the ISPOCD equivalent to the digital cognitive test Mindmore? A protocol for a randomised cross-over study including qualitative interviews with self-reported healthy seniors
- 2022
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 12:9, s. e062007-
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Tidskriftsartikel (refereegranskat)abstract
- Postoperative cognitive decline affects cognitive domains such as executive functions, memory, concentration and information processing. The analogue neuropsychological test developed by the International Study Group of Postoperative Cognitive Dysfunction (ISPOCD) is a well-established test for assessing cognitive performance. However, analogue tests are time-consuming, rarely cost-effective and can be at risk of administration bias. Digital solutions are comparable to analogue ones, have higher degrees of compliance and enable more standardised execution than analogue tests. Currently, there is a lack of recommendations for clinical evaluation of the patient’s cognition in the perioperative setting, standard care usually means no cognitive assessments prior or after the surgery. There is a need to find an equivalent neuropsychological test to the ISPOCD to make it accessible and easier to implement in a clinical context for perioperative patients. This study aims to examine how healthy seniors perform on two neuropsychological tests, analogue versus digital and measure equivalency between tests with correlation analysis.Methods and analysisThis study will use a randomised cross-over design, including qualitative interviews regarding test experiences. Healthy participants ≥60 years of age will be eligible to participate in the study. Cognitive function will be measured by using the ISPOCD test and the Mindmore digital test. The participants will self-report depressive symptoms with the Geriatric Depression Scale-15, user experience of the digital test using a modified version of the System Usability Scale and answer questionnaires targeting their experiences after the tests. Furthermore, according to the Swedish Quality of Recovery Scale, self-reported concentration difficulties will also be measured.Ethics and disseminationThe study has been approved by the Swedish Ethical Review Authority (Dnr 2021-05486-01) and will follow the principles outlined in the 1964 Helsinki Declaration and its later amendments. Results from this study will be disseminated in peer-reviewed journals, at scientific conferences, and in social media.Trial registration number2021-01095; ClinicalTrials.gov.
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