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1دورية أكاديمية
المؤلفون: Johnson, Robert T, Solanki, Reesha, Wostear, Finn, Ahmed, Sultan, Taylor, James CK, Rees, Jasmine, Abel, Geraad, McColl, James, Jørgensen, Helle F, Morris, Chris J, Bidula, Stefan, Warren, Derek T
مصطلحات موضوعية: aquaporin‐1, cell volume, matrix rigidity, piezo1, vascular smooth muscle, Extracellular Matrix, Humans, Myocytes, Smooth Muscle, Muscle, Smooth, Vascular, Ion Channels, Cell Size, Cells, Cultured, Animals, Hydrogels, Aorta
الوصف: Publication status: Published ; BACKGROUND AND PURPOSE: Decreased aortic compliance is a precursor to numerous cardiovascular diseases. Compliance is regulated by the rigidity of the aortic wall and the vascular smooth muscle cells (VSMCs). Extracellular matrix stiffening, observed during ageing, reduces compliance. In response to increased rigidity, VSMCs generate enhanced contractile forces that result in VSMC stiffening and a further reduction in compliance. Mechanisms driving VSMC response to matrix rigidity remain poorly defined. EXPERIMENTAL APPROACH: Human aortic-VSMCs were seeded onto polyacrylamide hydrogels whose rigidity mimicked either healthy (12 kPa) or aged/diseased (72 kPa) aortae. VSMCs were treated with pharmacological agents prior to agonist stimulation to identify regulators of VSMC volume regulation. KEY RESULTS: On pliable matrices, VSMCs contracted and decreased in cell area. Meanwhile, on rigid matrices VSMCs displayed a hypertrophic-like response, increasing in area and volume. Piezo1 activation stimulated increased VSMC volume by promoting calcium ion influx and subsequent activation of PKC and aquaporin-1. Pharmacological blockade of this pathway prevented the enhanced VSMC volume response on rigid matrices whilst maintaining contractility on pliable matrices. Importantly, both piezo1 and aquaporin-1 gene expression were up-regulated during VSMC phenotypic modulation in atherosclerosis and after carotid ligation. CONCLUSIONS AND IMPLICATIONS: In response to extracellular matrix rigidity, VSMC volume is increased by a piezo1/PKC/aquaporin-1 mediated pathway. Pharmacological targeting of this pathway specifically blocks the matrix rigidity enhanced VSMC volume response, leaving VSMC contractility on healthy mimicking matrices intact. Importantly, upregulation of both piezo1 and aquaporin-1 gene expression is observed in disease relevant VSMC phenotypes.
وصف الملف: text/xml; application/pdf
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2دورية أكاديمية
المؤلفون: Johnson, Robert T., Solanki, Reesha, Wostear, Finn, Ahmed, Sultan, Taylor, James C. K., Rees, Jasmine, Abel, Geraad, McColl, James, Jørgensen, Helle F., Morris, Chris J., Bidula, Stefan, Warren, Derek T.
المساهمون: British Heart Foundation, Biotechnology and Biological Sciences Research Council
المصدر: British Journal of Pharmacology ; volume 181, issue 11, page 1576-1595 ; ISSN 0007-1188 1476-5381
الوصف: Background and Purpose Decreased aortic compliance is a precursor to numerous cardiovascular diseases. Compliance is regulated by the rigidity of the aortic wall and the vascular smooth muscle cells (VSMCs). Extracellular matrix stiffening, observed during ageing, reduces compliance. In response to increased rigidity, VSMCs generate enhanced contractile forces that result in VSMC stiffening and a further reduction in compliance. Mechanisms driving VSMC response to matrix rigidity remain poorly defined. Experimental Approach Human aortic‐VSMCs were seeded onto polyacrylamide hydrogels whose rigidity mimicked either healthy (12 kPa) or aged/diseased (72 kPa) aortae. VSMCs were treated with pharmacological agents prior to agonist stimulation to identify regulators of VSMC volume regulation. Key Results On pliable matrices, VSMCs contracted and decreased in cell area. Meanwhile, on rigid matrices VSMCs displayed a hypertrophic‐like response, increasing in area and volume. Piezo1 activation stimulated increased VSMC volume by promoting calcium ion influx and subsequent activation of PKC and aquaporin‐1. Pharmacological blockade of this pathway prevented the enhanced VSMC volume response on rigid matrices whilst maintaining contractility on pliable matrices. Importantly, both piezo1 and aquaporin‐1 gene expression were up‐regulated during VSMC phenotypic modulation in atherosclerosis and after carotid ligation. Conclusions and Implications In response to extracellular matrix rigidity, VSMC volume is increased by a piezo1/PKC/aquaporin‐1 mediated pathway. Pharmacological targeting of this pathway specifically blocks the matrix rigidity enhanced VSMC volume response, leaving VSMC contractility on healthy mimicking matrices intact. Importantly, upregulation of both piezo1 and aquaporin‐1 gene expression is observed in disease relevant VSMC phenotypes.
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3دورية أكاديمية
المؤلفون: Johnson, Robert T, Solanki, Reesha, Wostear, Finn, Ahmed, Sultan, Taylor, James CK, Rees, Jasmine, Abel, Geraad, Mccoll, James, Jorgensen, Helle F, Morris, Chris J, Bidula, Stefan, Warren, Derek T
المصدر: British Journal of Pharmacology (2023) (In press).
مصطلحات موضوعية: Aquaporin-1, cell volume, matrix rigidity, piezo1, vascular smooth muscle
الوصف: BACKGROUND AND PURPOSE: Decreased aortic compliance is a precursor to numerous cardiovascular diseases. Compliance is regulated by the rigidity of the aortic wall and the vascular smooth muscle cells (VSMCs). Extracellular matrix stiffening, observed during ageing, reduces compliance. In response to increased rigidity, VSMCs generate enhanced contractile forces that result in VSMC stiffening and a further reduction in compliance. Mechanisms driving VSMC response to matrix rigidity remain poorly defined. EXPERIMENTAL APPROACH: Human aortic-VSMCs were seeded onto polyacrylamide hydrogels whose rigidity mimicked either healthy (12 kPa) or aged/diseased (72 kPa) aortae. VSMCs were treated with pharmacological agents prior to agonist stimulation to identify regulators of VSMC volume regulation. KEY RESULTS: On pliable matrices, VSMCs contracted and decreased in cell area. Meanwhile, on rigid matrices VSMCs displayed a hypertrophic-like response, increasing in area and volume. Piezo1 activation stimulated increased VSMC volume by promoting calcium ion influx and subsequent activation of PKC and aquaporin-1. Pharmacological blockade of this pathway prevented the enhanced VSMC volume response on rigid matrices whilst maintaining contractility on pliable matrices. Importantly, both piezo1 and aquaporin-1 gene expression were up-regulated during VSMC phenotypic modulation in atherosclerosis and after carotid ligation. CONCLUSIONS AND IMPLICATIONS: In response to extracellular matrix rigidity, VSMC volume is increased by a piezo1/PKC/aquaporin-1 mediated pathway. Pharmacological targeting of this pathway specifically blocks the matrix rigidity enhanced VSMC volume response, leaving VSMC contractility on healthy mimicking matrices intact. Importantly, upregulation of both piezo1 and aquaporin-1 gene expression is observed in disease relevant VSMC phenotypes.
وصف الملف: text
العلاقة: https://discovery.ucl.ac.uk/id/eprint/10186878/1/Piezo1%20mediated%20regulation%20of%20smooth%20muscle%20cell%20volume.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10186878Test/
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4دورية أكاديمية
المؤلفون: Proestakis, Ermis, Christensen, Helle F., Meireles, Leonardo T. P., Storebø, Einar M., Shamsolhodaei, Amirhossein, Orlander, Tobias
المصدر: Geophysical Prospecting ; volume 72, issue 2, page 733-751 ; ISSN 0016-8025 1365-2478
الوصف: Elastic wave velocities of compressional and shear waves propagating through sedimentary rocks are often coupled with information of bulk density to derive the rock stiffness. Acquiring the transit time of compressional and shear waves often involves manual picking of wave arrival times from wave trains recorded in the laboratory or by well‐logging tools. Picking the compressional wave arrival time is commonly accepted as straightforward. Oppositely, detecting the shear wave arrival and picking its arrival time is often troublesome because the transmitted shear wave partly converts to compressional waves and back to a secondary shear wave, concealing the transmitted shear wave arrival in the wave train. In laboratory settings, we illustrate the difficulty of shear wave detection in wave trains recorded on highly porous chalk plug samples from the Danish North Sea Basin. Wave trains were recorded on plugs dry, Tap‐water or Isopar‐L saturated during uniaxial strain compaction. The recorded shear wave trains showed two distinct features, which could be interpreted as the transmitted shear wave first arrival; we denoted them as early and late arrivals. However, as only one feature can mark the arrival of the transmitted shear wave, we propose a semi‐empirical disclosure strategy combining a graphical representation of stacked wave trains with rock physical modelling. By stacking recorded wave trains in a graphical strain–time–amplitude domain, we demonstrate that an early shear wave feature marks a converted shear to compressional to shear wave and not the transmitted shear wave. We used physical modelling to identify early shear wave features and illustrate the consequences of adopting a falsely interpreted shear wave on stiffness properties.
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5دورية أكاديمية
المؤلفون: Harman, Jennifer L., Jørgensen, Helle F.
المساهمون: British Heart Foundation
المصدر: British Journal of Pharmacology ; volume 176, issue 19, page 3741-3753 ; ISSN 0007-1188 1476-5381
الوصف: Events responsible for cardiovascular mortality and morbidity are predominantly caused by rupture of “vulnerable” atherosclerotic lesions. Vascular smooth muscle cells (VSMCs) play a key role in atherogenesis and have historically been considered beneficial for plaque stability. VSMCs constitute the main cellular component of the protective fibrous cap within lesions and are responsible for synthesising strength‐giving extracellular matrix components. However, lineage‐tracing experiments in mouse models of atherosclerosis have shown that, in addition to the fibrous cap, VSMCs also give rise to many of the cell types found within the plaque core. In particular, VSMCs generate a substantial fraction of lipid‐laden foam cells, and VSMC‐derived cells expressing markers of macrophages, osteochondrocyte, and mesenchymal stem cells have been observed within lesions. Here, we review recent studies that have changed our perspective on VSMC function in atherosclerosis and discuss how VSMCs could be targeted to increase plaque stability.
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6دورية أكاديمية
المؤلفون: McEvoy, Fintan J., Proschowsky, Helle F., Müller, Anna V., Moorman, Lilah, Bender‐Koch, Johan, Svalastoga, Eiliv L., Frellsen, Jes, Nielsen, Dorte H.
المصدر: Veterinary Radiology & Ultrasound ; volume 62, issue 4, page 387-393 ; ISSN 1058-8183 1740-8261
الوصف: Reports of machine learning implementations in veterinary imaging are infrequent but changes in machine learning architecture and access to increased computing power will likely prompt increased interest. This diagnostic accuracy study describes a particular form of machine learning, a deep learning convolution neural network (ConvNet) for hip joint detection and classification of hip dysplasia from ventro‐dorsal (VD) pelvis radiographs submitted for hip dysplasia screening. 11,759 pelvis images were available together with their Fédération Cynologique Internationale (FCI) scores. The dataset was dicotomized into images showing no signs of hip dysplasia (FCI grades “A” and “B”, the “A‐B” group) and hips showing signs of dysplasia (FCI grades “C”, “D,” and “E”, the “C‐E” group). In a transfer learning approach, an existing pretrained ConvNet was fine‐tuned to provide models to recognize hip joints in VD pelvis images and to classify them according to their FCI score grouping. The results yielded two models. The first was successful in detecting hip joints in the VD pelvis images (intersection over union of 85%). The second yielded a sensitivity of 0.53, a specificity of 0.92, a positive predictive value of 0.91, and a negative predictive value of 0.81 for the classification of detected hip joints as being in the “C‐E” group. ConvNets and transfer learning are applicable to veterinary imaging. The models obtained have potential to be a tool to aid in hip screening protocols if hip dysplasia classification performance was improved through access to more data and possibly by model optimization.
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7دورية أكاديمية
المؤلفون: Helle, F., Dahl, T. D., Chatziantoniou, C.
المصدر: Acta Physiologica ; volume 211, issue 2, page 260-267 ; ISSN 1748-1708 1748-1716
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8دورية أكاديمية
المؤلفون: Harman, Jennifer L, Jørgensen, Helle F
مصطلحات موضوعية: Animals, Humans, Muscle, Smooth, Vascular, Myocytes, Smooth Muscle, Plaque, Atherosclerotic
الوصف: Events responsible for cardiovascular mortality and morbidity are predominantly caused by rupture of "vulnerable" atherosclerotic lesions. Vascular smooth muscle cells (VSMCs) play a key role in atherogenesis and have historically been considered beneficial for plaque stability. VSMCs constitute the main cellular component of the protective fibrous cap within lesions and are responsible for synthesising strength-giving extracellular matrix components. However, lineage-tracing experiments in mouse models of atherosclerosis have shown that, in addition to the fibrous cap, VSMCs also give rise to many of the cell types found within the plaque core. In particular, VSMCs generate a substantial fraction of lipid-laden foam cells, and VSMC-derived cells expressing markers of macrophages, osteochondrocyte, and mesenchymal stem cells have been observed within lesions. Here, we review recent studies that have changed our perspective on VSMC function in atherosclerosis and discuss how VSMCs could be targeted to increase plaque stability. ; JLH and HFJ are supported by the British Heart Foundation (FS/15/62/32032, RM/13/3/30159, RE/13/6/30180, CH/ 20000003).
وصف الملف: Print-Electronic; application/pdf; application/vnd.openxmlformats-officedocument.wordprocessingml.document
الإتاحة: https://doi.org/10.17863/CAM.40942Test
https://www.repository.cam.ac.uk/handle/1810/293829Test -
9دورية أكاديمية
المؤلفون: Fournier, C., Hoffmann, T. W., Morel, V., Descamps, V., Dubuisson, J., Brochot, E., Francois, C., Duverlie, G., Castelain, S., Helle, F.
المساهمون: Conseil Regional de Picardie
المصدر: Journal of Viral Hepatitis ; volume 25, issue 1, page 63-71 ; ISSN 1352-0504 1365-2893
الوصف: Summary Hepatitis C virus ( HCV ) is a human hepatotropic virus, but many hepatoma cell lines are not permissive to this virus. In a previous study, we observed that SNU ‐182, SNU ‐398 and SNU ‐449 hepatoma cell lines were nonpermissive to HCV . To understand the nonpermissivity, we evaluated the ability of each cell line to support the different steps of HCV life cycle (entry, replication and production of infectious particles). Using retroviral pseudoparticles pseudotyped with HCV envelope proteins and recombinant HCV produced in cell culture, we observed that low level or absence of claudin‐1 (CLDN1) expression limited the viral entry process in SNU ‐182 and SNU ‐398 cells, respectively. Our results also showed that supplementation of the three cell lines with miR‐122 partly restored the replication of a JFH 1 HCV replicon. Finally, we observed that expression of apolipoprotein E (ApoE) was very low or undetectable in the three cell lines and that its ectopic expression permits the production of infectious viral particles in SNU ‐182 and SNU ‐398 cells but not in SNU ‐449 cells. Nevertheless, the supplementation of SNU ‐182, SNU ‐398 and SNU ‐449 cells with CLDN1, miR‐122 and ApoE was not sufficient to render these cells as permissive as HuH‐7 cells. Thus, these cell lines could serve as cell culture models for functional studies on the role of CLDN1, miR‐122 and ApoE in HCV life cycle but also for the identification of new restriction and/or dependency host factors essential for HCV infection.
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10دورية أكاديمية
المؤلفون: Helle, F., Karlsen, T. V., Tenstad, O., Titze, J., Wiig, H.
المصدر: Acta Physiologica ; volume 207, issue 3, page 577-581 ; ISSN 1748-1708 1748-1716
الوصف: Aims Recent data indicate that the skin of rats on a high‐salt diet is able to accumulate Na + without commensurate water. This extrarenal mechanism of Na + homoeostasis could affect skin vasoregulation. We hypothesized that the major resistance vessel of rat skin, the pre‐capillary arterioles, has increased vasoreactivity within the physiological range of circulating ANG II , a hormone relevant to salt‐sensitive hypertension. Methods and results Skin arterioles from skin and muscle were isolated using the agar‐infusion technique. Vessels from rats fed high‐salt and low‐salt diet had similar lumen diameter and media area/lumen area ratio. Contractile sensitivity to ANG II was increased in skin vessels from high‐salt vessels at all doses tested starting at 10 −10 m ( P < 0.01). Pre‐capillary arterioles from muscle displayed similar contractions to ANG II , independent of the diet. As ANG II and the renin–angiotensin system are strongly involved in salt conservation, we explored whether vasoreactivity for noradrenaline was increased as well, because this is a functionally unrelated hormone. At low doses, contractions were similar, but at 10 −5 and 10 −4 m , noradrenaline produced stronger contractions in skin vessels from high‐salt compared with low‐salt rats ( P < 0.01). Conclusions Our data demonstrate significantly increased hormonal vasoreactivity of skin vessels from rats on a high‐salt diet, which could increase peripheral resistance in many situations and contribute to higher pressure in salt‐sensitive hypertension. As vessels from adjacent muscle were unaffected, we raise the interesting possibility that increased vasoreactivity in the skin could be linked to osmotically inactive Na + accumulation.
