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用于可视化和评估针对动脉粥样硬化的白细胞介素-1β靶向治疗的弹性蛋白特异性磁共振探针。

Elastin-specific MR probe for visualization and evaluation of an interleukin-1β targeted therapy for atherosclerosis.

机构信息

Department of Radiology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117, Berlin, Germany.

Division 1.5 Protein Analysis, Federal Institute for Materials Research and Testing (BAM), Richard-Willstätter-Str. 11, 12489, Berlin, Germany.

出版信息

Sci Rep. 2024 Sep 4;14(1):20648. doi: 10.1038/s41598-024-71716-5.

Abstract

Atherosclerosis is a chronic inflammatory condition of the arteries and represents the primary cause of various cardiovascular diseases. Despite ongoing progress, finding effective anti-inflammatory therapeutic strategies for atherosclerosis remains a challenge. Here, we assessed the potential of molecular magnetic resonance imaging (MRI) to visualize the effects of 01BSUR, an anti-interleukin-1β monoclonal antibody, for treating atherosclerosis in a murine model. Male apolipoprotein E-deficient mice were divided into a therapy group (01BSUR, 2 × 0.3 mg/kg subcutaneously, n = 10) and control group (no treatment, n = 10) and received a high-fat diet for eight weeks. The plaque burden was assessed using an elastin-targeted gadolinium-based contrast probe (0.2 mmol/kg intravenously) on a 3 T MRI scanner. T1-weighted imaging showed a significantly lower contrast-to-noise (CNR) ratio in the 01BSUR group (pre: 3.93042664; post: 8.4007067) compared to the control group (pre: 3.70679168; post: 13.2982156) following administration of the elastin-specific MRI probe (p < 0.05). Histological examinations demonstrated a significant reduction in plaque size (p < 0.05) and a significant decrease in plaque elastin content (p < 0.05) in the treatment group compared to control animals. This study demonstrated that 01BSUR hinders the progression of atherosclerosis in a mouse model. Using an elastin-targeted MRI probe, we could quantify these therapeutic effects in MRI.

摘要

动脉粥样硬化是一种慢性动脉炎症性疾病,是各种心血管疾病的主要病因。尽管在不断取得进展,但寻找有效的抗动脉粥样硬化炎症治疗策略仍然是一个挑战。在这里,我们评估了分子磁共振成像(MRI)在评估抗白细胞介素-1β单克隆抗体 01BSUR 治疗动脉粥样硬化在小鼠模型中的疗效的潜力。雄性载脂蛋白 E 缺陷小鼠分为治疗组(01BSUR,2×0.3 mg/kg 皮下注射,n=10)和对照组(无治疗,n=10),并接受高脂饮食 8 周。斑块负荷通过静脉注射弹性蛋白靶向钆基对比探针(0.2 mmol/kg)在 3T MRI 扫描仪上进行评估。T1 加权成像显示,与对照组(预处理:3.70679168;后处理:13.2982156)相比,01BSUR 组(预处理:3.93042664;后处理:8.4007067)的对比噪声比(CNR)明显更低(p<0.05)。组织学检查显示,与对照组相比,治疗组的斑块大小显著减小(p<0.05),斑块弹性蛋白含量显著降低(p<0.05)。这项研究表明,01BSUR 可抑制小鼠模型中动脉粥样硬化的进展。使用弹性蛋白靶向 MRI 探针,我们可以在 MRI 中定量这些治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e23e/11375012/0ef50a50c32e/41598_2024_71716_Fig1_HTML.jpg

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