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

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.

Keywords: Atherosclerosis; Elastin; Interleukin-1beta; Molecular imaging; Plaque.

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Apolipoproteins E / deficiency
  • Atherosclerosis* / diagnostic imaging
  • Atherosclerosis* / drug therapy
  • Atherosclerosis* / metabolism
  • Contrast Media / chemistry
  • Diet, High-Fat
  • Disease Models, Animal
  • Elastin* / metabolism
  • Gadolinium / chemistry
  • Gadolinium / pharmacology
  • Interleukin-1beta* / metabolism
  • Magnetic Resonance Imaging / methods
  • Male
  • Mice
  • Plaque, Atherosclerotic / diagnostic imaging
  • Plaque, Atherosclerotic / drug therapy

Substances

  • Antibodies, Monoclonal
  • Apolipoproteins E
  • Contrast Media
  • Elastin
  • Gadolinium
  • Interleukin-1beta