| 1. |
- Good, Elin, 1983-, et al.
(författare)
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Changes in natural killer and T lymphocyte phenotypes in response to cardiovascular risk management
- 2023
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- The pro-inflammatory and regulatory roles of T lymphocytes in atherosclerosis are well established but less is known about natural killer (NK) cells and natural killer T (NKT)-like cells. The effects of cardiovascular risk management on the phenotypes of these cells are unknown. To assess changes in NK cell and lymphocyte phenotypes and circulating inflammatory proteins in response to cardiovascular risk management in patients with carotid atherosclerosis. Fifty patients were included in a prospective clinical study. Measurements were at baseline and after 12 months of cardiovascular risk management. Circulating NK, NKT-like and T lymphocyte subpopulations were phenotyped by multi-colour flow cytometry. Proximity extension assay was performed for 176 plasma proteins associated with inflammation and cardiovascular disease. At 12 months there were significant reductions in LDL (P=0.001) and blood pressure (P=0.028). NK cells responded with a reduction in pro-inflammatory (NKG2C(+)) cells (P=0.0003), an increase in anti-inflammatory (NKG2A(+)) cells (P=0.032), and a reduction in terminally differentiated (CD57(+)) NK cells. NKT-like cells showed a similar decrease in terminally differentiated subpopulations (P=0.000002). Subpopulations of T helper cells exhibited a significant reduction in central memory (P=1.09x10(-8)) and a significant increase in CD4(+) naive- (P=0.0008) and effector memory T cells (P=0.006). The protein analysis indicated that cardiovascular risk management affects proteins involved in the inflammatory NF-kappa B pathway. The consistent decrease in senescent phenotypes of NK, NKT-like and CD4(+) cells with a concomitant increase in more naive, phenotypes suggests a change towards a less pro-inflammatory lymphocyte profile in response to cardiovascular risk management.Trial registry name: CARotid MRI of Atherosclerosis (CARMA). ClinicalTrials.gov identifier NCT04835571 (08/04/2021). https://www.clinicaltrials.gov/study/NCT04835571.
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| 2. |
- Good, Elin, 1983-
(författare)
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Interrogating Atherosclerotic Plaque Biology Through Responses to Cardiovascular Risk Management and Imaging
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Atherosclerosis causes more deaths than any other disease worldwide, and the cause of death is most commonly a rupture of a vulnerable atherosclerotic plaque, resulting in a thrombotic event in the heart or brain. The major risk factors for plaque progression are well known, but all the mechanisms that drive atherosclerotic plaques towards catastrophic events are not yet fully elucidated. This thesis revolves around the atherosclerotic plaque; how plaques can be analysed using cardiovascular magnetic resonance imaging and the study of biological responses to cardiovascular risk management. In Study I we interrogated the quality of cardiovascular risk management in patients diagnosed with high-grade carotid stenosis and found that cardiovascular risk management was deficient in all aspects, despite the very high risk for events in these patients. Thus, we designed the next two studies to address the unmet clinical need for improved cardiovascular risk management in patients with carotid atherosclerosis while at the same time asking mechanistic questions about the effect of this approach on lymphocyte phenotypes (Study II) and on plaque composition (Study III). In Study II, the effect of cardiovascular risk management on Natural Killer cell, Natural Killer T cell and T lymphocyte subpopulations were studied in patients with carotid atherosclerosis. Our results show a polarisation away from a senescent phenotype towards more naïve i.e., juvenile cell types suggesting a transition towards a possibly less pro-inflammatory lymphocyte profile. In Study III, we applied a newly developed quantitative Dixon MRI technique to the quantification of lipid rich necrotic core and hemorrhage inside atherosclerotic plaques. Employing this technique, we explored the relationships between these high-risk plaque compositional features and circulating lipoproteins as they changed over time in response to cardiovascular risk management. In the current study there was no evidence for such a linear relationship. To further study the associations between inflammation and quantitative plaque measurements we explored in Study IV the relationship between inflammation in atherosclerotic plaques as measured by 18F-FDG uptake and features of high-risk plaque as measured by quantitative Dixon MRI. To facilitate the use of carotid MRI in larger cohorts we developed in Study V a technique for the segmentation of the carotid artery using supervised machine learning. Taken together these studies describe the importance of cardiovascular risk management, the complexity of atherosclerotic plaque biology and they propose new strategies for quantitative plaque imaging.
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| 3. |
- Sherrell, Peter, 1986-, et al.
(författare)
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Rational Design of a Conductive Collagen Heart Patch
- 2017
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Ingår i: Macromolecular Bioscience. - : Wiley-VCH Verlagsgesellschaft. - 1616-5187 .- 1616-5195. ; 17:7
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Tidskriftsartikel (refereegranskat)abstract
- Cardiovascular diseases, including myocardial infarction, are the cause of significant morbidity and mortality globally. Tissue engineering is a key emerging treatment method for supporting and repairing the cardiac scar tissue caused by myocardial infarction. Creating cell supportive scaffolds that can be directly implanted on a myocardial infarct is an attractive solution. Hydrogels made of collagen are highly biocompatible materials that can be molded into a range of shapes suitable for cardiac patch applications. The addition of mechanically reinforcing materials, carbon nanotubes, at subtoxic levels allows for the collagen hydrogels to be strengthened, up to a toughness of 30 J m-1 and a two to threefold improvement in Youngs' modulus, thus improving their viability as cardiac patch materials. The addition of carbon nanotubes is shown to be both nontoxic to stem cells, and when using single-walled carbon nanotubes, supportive of live, beating cardiac cells, providing a pathway for the further development of a cardiac patch.
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| 4. |
- Ziegler, Magnus, 1990-
(författare)
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Improving Assessments of Hemodynamics and Vascular Disease
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Blood vessels are more than simple pipes, passively enabling blood to pass through them. Their form and function are dynamic, changing with both aging and disease. This process involves a feedback loop wherein changes to the shape of a blood vessel affect the hemodynamics, causing yet more structural adaptation. This feedback loop is driven in part by the hemodynamic forces generated by the blood flow, and the distribution and strength of these forces appear to play a role in the initiation, progression, severity, and the outcome of vascular diseases.Magnetic Resonance Imaging (MRI) offers a unique platform for investigating both the form and function of the vascular system. The form of the vascular system can be examined using MR-based angiography, to generate detailed geometric analyses, or through quantitative techniques for measuring the composition of the vessel wall and atherosclerotic plaques. To complement these analyses, 4D Flow MRI can be used to quantify the functional aspect of the vascular system, by generating a full time-resolved three-dimensional velocity field that represents the blood flow.This thesis aims to develop and evaluate new methods for assessing vascular disease using novel hemodynamic markers generated from 4D Flow MRI and quantitative MRI data towards the larger goal of a more comprehensive non-invasive examination oriented towards vascular disease. In Paper I, we developed and evaluated techniques to quantify flow stasis in abdominal aortic aneurysms to measure this under-explored aspect of aneurysmal hemodynamics. In Paper II, the distribution and intensity of turbulence in the aorta was quantified in both younger and older men to understand how aging changes this aspect of hemodynamics. A method to quantify the stresses generated by turbulence that act on the vessel wall was developed and evaluated using simulated flow data in Paper III, and in Paper V this method was utilized to examine the wall stresses of the carotid artery. The hemodynamics of vascular disease cannot be uncoupled from the anatomical changes the vessel wall undergoes, and therefore Paper IV developed and evaluated a semi-automatic method for quantifying several aspects of vessel wall composition. These developments, taken together, help generate more valuable information from imaging data, and can be pooled together with other methods to form a more comprehensive non-invasive examination for vascular disease.
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| 5. |
- Ziegler, Magnus, et al.
(författare)
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Towards Automated Quantification of Vessel Wall Composition Using MRI
- 2020
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Ingår i: Journal of Magnetic Resonance Imaging. - : WILEY. - 1053-1807 .- 1522-2586. ; 52:3, s. 710-719
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Tidskriftsartikel (refereegranskat)abstract
- Background MRI can be used to generate fat fraction (FF) and R2* data, which have been previously shown to characterize the plaque compositional features lipid-rich necrotic core (LRNC) and intraplaque hemorrhage (IPH) in the carotid arteries (CAs). Previously, these data were extracted from CA plaques using time-consuming manual analyses. Purpose To design and demonstrate a method for segmenting the CA and extracting data describing the composition of the vessel wall. Study Type Prospective. Subjects 31 subjects from the Swedish CArdioPulmonary bioImage Study (SCAPIS). Field Strength/Sequences T-1-weighted (T1W) quadruple inversion recovery, contrast-enhanced MR angiography (CE-MRA), and 4-point Dixon data were acquired at 3T. Assessment The vessel lumen of the CA was automatically segmented using support vector machines (SVM) with CE-MRA data, and the vessel wall region was subsequently delineated. Automatically generated segmentations were quantitatively measured and three observers visually compared the segmentations to manual segmentations performed on T(1)w images. Dixon data were used to generate FF and R2* maps. Both manually and automatically generated segmentations of the CA and vessel wall were used to extract compositional data. Statistical Tests Two-tailedt-tests were used to examine differences between results generated using manual and automated analyses, and among different configurations of the automated method. Interobserver agreement was assessed with Fleiss kappa. Results Automated segmentation of the CA using SVM had a Dice score of 0.89 +/- 0.02 and true-positive ratio 0.93 +/- 0.03 when compared against ground truth, and median qualitative score of 4/5 when assessed visually by multiple observers. Vessel wall regions of 0.5 and 1 mm yielded compositional information similar to that gained from manual analyses. Using the 0.5 mm vessel wall region, the mean difference was 0.1 +/- 2.5% considering FF and 1.1 +/- 5.7[1/s] for R2*. Level of Evidence 1. Technical Efficacy Stage 1. J. Magn. Reson. Imaging 2020;52:710-719.
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