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

弹性蛋白特异性磁共振探头用于动脉粥样硬化白细胞介素-1β靶向治疗的可视化和评估

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作者:Dilyana Branimirova Mangarova, Carolin Reimann, Jan Ole Kaufmann, Jana Möckel, Avan Kader, Lisa Christine Adams, Antje Ludwig, David Onthank, Simon Robinson, Uwe Karst, Rebecca Helmer, Rene Botnar, Bernd Hamm, Marcus Richard Makowski #, Julia Brangsch #

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.

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