Julia Brangsch, Carolin Reimann, Jan Ole Kaufmann, Lisa Christine Adams, David Onthank, Christa Thöne-Reineke, Simon Robinson, Marco Wilke, Michael Weller, Rebecca Buchholz, Uwe Karst, Rene Botnar, Bernd Hamm, Marcus Richard Makowski
{"title":"靶向白介素-1β在小鼠主动脉瘤模型中的抗炎作用的分子磁共振成像无创定量研究。","authors":"Julia Brangsch, Carolin Reimann, Jan Ole Kaufmann, Lisa Christine Adams, David Onthank, Christa Thöne-Reineke, Simon Robinson, Marco Wilke, Michael Weller, Rebecca Buchholz, Uwe Karst, Rene Botnar, Bernd Hamm, Marcus Richard Makowski","doi":"10.1177/1536012120961875","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Molecular-MRI is a promising imaging modality for the assessment of abdominal aortic aneurysms (AAAs). Interleukin-1β (IL-1β) represents a new therapeutic tool for AAA-treatment, since pro-inflammatory cytokines are key-mediators of inflammation. This study investigates the potential of molecular-MRI to evaluate therapeutic effects of an anti-IL-1β-therapy on AAA-formation in a mouse-model.</p><p><strong>Methods: </strong>Osmotic-minipumps were implanted in apolipoprotein-deficient-mice (N = 27). One group (Ang-II+01BSUR group, n = 9) was infused with angiotensin-II (Ang-II) for 4 weeks and received an anti-murine IL-1β-antibody (01BSUR) 3 times. One group (Ang-II-group, n = 9) was infused with Ang-II for 4 weeks but received no treatment. Control-group (n = 9) was infused with saline and received no treatment. MR-imaging was performed using an elastin-specific gadolinium-based-probe (0.2 mmol/kg).</p><p><strong>Results: </strong>Mice of the Ang-II+01BSUR-group showed a lower aortic-diameter compared to mice of the Ang-II-group and control mice (p < 0.05). Using the elastin-specific-probe, a significant decrease in elastin-destruction was observed in mice of the Ang-II+01BSUR-group. In vivo MR-measurements correlated well with histopathology (y = 0.34x-13.81, R<sup>2</sup> = 0.84, p < 0.05), ICP-MS (y = 0.02x+2.39; R<sup>2</sup> = 0.81, p < 0.05) and LA-ICP-MS. Immunofluorescence and western-blotting confirmed a reduced IL-1β-expression.</p><p><strong>Conclusions: </strong>Molecular-MRI enables the early visualization and quantification of the anti-inflammatory-effects of an IL-1β-inhibitor in a mouse-model of AAAs. Responders and non-responders could be identified early after the initiation of the therapy using molecular-MRI.</p>","PeriodicalId":18855,"journal":{"name":"Molecular Imaging","volume":"19 ","pages":"1536012120961875"},"PeriodicalIF":2.2000,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1536012120961875","citationCount":"2","resultStr":"{\"title\":\"Molecular MR-Imaging for Noninvasive Quantification of the Anti-Inflammatory Effect of Targeting Interleukin-1β in a Mouse Model of Aortic Aneurysm.\",\"authors\":\"Julia Brangsch, Carolin Reimann, Jan Ole Kaufmann, Lisa Christine Adams, David Onthank, Christa Thöne-Reineke, Simon Robinson, Marco Wilke, Michael Weller, Rebecca Buchholz, Uwe Karst, Rene Botnar, Bernd Hamm, Marcus Richard Makowski\",\"doi\":\"10.1177/1536012120961875\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Molecular-MRI is a promising imaging modality for the assessment of abdominal aortic aneurysms (AAAs). Interleukin-1β (IL-1β) represents a new therapeutic tool for AAA-treatment, since pro-inflammatory cytokines are key-mediators of inflammation. This study investigates the potential of molecular-MRI to evaluate therapeutic effects of an anti-IL-1β-therapy on AAA-formation in a mouse-model.</p><p><strong>Methods: </strong>Osmotic-minipumps were implanted in apolipoprotein-deficient-mice (N = 27). One group (Ang-II+01BSUR group, n = 9) was infused with angiotensin-II (Ang-II) for 4 weeks and received an anti-murine IL-1β-antibody (01BSUR) 3 times. One group (Ang-II-group, n = 9) was infused with Ang-II for 4 weeks but received no treatment. Control-group (n = 9) was infused with saline and received no treatment. MR-imaging was performed using an elastin-specific gadolinium-based-probe (0.2 mmol/kg).</p><p><strong>Results: </strong>Mice of the Ang-II+01BSUR-group showed a lower aortic-diameter compared to mice of the Ang-II-group and control mice (p < 0.05). Using the elastin-specific-probe, a significant decrease in elastin-destruction was observed in mice of the Ang-II+01BSUR-group. In vivo MR-measurements correlated well with histopathology (y = 0.34x-13.81, R<sup>2</sup> = 0.84, p < 0.05), ICP-MS (y = 0.02x+2.39; R<sup>2</sup> = 0.81, p < 0.05) and LA-ICP-MS. Immunofluorescence and western-blotting confirmed a reduced IL-1β-expression.</p><p><strong>Conclusions: </strong>Molecular-MRI enables the early visualization and quantification of the anti-inflammatory-effects of an IL-1β-inhibitor in a mouse-model of AAAs. Responders and non-responders could be identified early after the initiation of the therapy using molecular-MRI.</p>\",\"PeriodicalId\":18855,\"journal\":{\"name\":\"Molecular Imaging\",\"volume\":\"19 \",\"pages\":\"1536012120961875\"},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2020-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1177/1536012120961875\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Imaging\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/1536012120961875\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Imaging","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/1536012120961875","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
Molecular MR-Imaging for Noninvasive Quantification of the Anti-Inflammatory Effect of Targeting Interleukin-1β in a Mouse Model of Aortic Aneurysm.
Background: Molecular-MRI is a promising imaging modality for the assessment of abdominal aortic aneurysms (AAAs). Interleukin-1β (IL-1β) represents a new therapeutic tool for AAA-treatment, since pro-inflammatory cytokines are key-mediators of inflammation. This study investigates the potential of molecular-MRI to evaluate therapeutic effects of an anti-IL-1β-therapy on AAA-formation in a mouse-model.
Methods: Osmotic-minipumps were implanted in apolipoprotein-deficient-mice (N = 27). One group (Ang-II+01BSUR group, n = 9) was infused with angiotensin-II (Ang-II) for 4 weeks and received an anti-murine IL-1β-antibody (01BSUR) 3 times. One group (Ang-II-group, n = 9) was infused with Ang-II for 4 weeks but received no treatment. Control-group (n = 9) was infused with saline and received no treatment. MR-imaging was performed using an elastin-specific gadolinium-based-probe (0.2 mmol/kg).
Results: Mice of the Ang-II+01BSUR-group showed a lower aortic-diameter compared to mice of the Ang-II-group and control mice (p < 0.05). Using the elastin-specific-probe, a significant decrease in elastin-destruction was observed in mice of the Ang-II+01BSUR-group. In vivo MR-measurements correlated well with histopathology (y = 0.34x-13.81, R2 = 0.84, p < 0.05), ICP-MS (y = 0.02x+2.39; R2 = 0.81, p < 0.05) and LA-ICP-MS. Immunofluorescence and western-blotting confirmed a reduced IL-1β-expression.
Conclusions: Molecular-MRI enables the early visualization and quantification of the anti-inflammatory-effects of an IL-1β-inhibitor in a mouse-model of AAAs. Responders and non-responders could be identified early after the initiation of the therapy using molecular-MRI.
Molecular ImagingBiochemistry, Genetics and Molecular Biology-Biotechnology
自引率
3.60%
发文量
21
期刊介绍:
Molecular Imaging is a peer-reviewed, open access journal highlighting the breadth of molecular imaging research from basic science to preclinical studies to human applications. This serves both the scientific and clinical communities by disseminating novel results and concepts relevant to the biological study of normal and disease processes in both basic and translational studies ranging from mice to humans.