Everolimus-eluting stents stabilize plaque inflammation in vivo: assessment by intravascular fluorescence molecular imaging

Eur Heart J Cardiovasc Imaging. 2017 May 1;18(5):510-518. doi: 10.1093/ehjci/jew228.

Abstract

Aims: Inflammation drives atherosclerosis complications and is a promising therapeutic target for plaque stabilization. At present, it is unknown whether local stenting approaches can stabilize plaque inflammation in vivo. Here, we investigate whether everolimus-eluting stents (EES) can locally suppress plaque inflammatory protease activity in vivo using intravascular near-infrared fluorescence (NIRF) molecular imaging.

Methods and results: Balloon-injured, hyperlipidaemic rabbits with atherosclerosis received non-overlapping EES and bare metal stents (BMS) placement into the infrarenal aorta (n = 7 EES, n = 7 BMS, 3.5 mm diameter x 12 mm length). Four weeks later, rabbits received an injection of the cysteine protease-activatable NIRF imaging agent Prosense VM110. Twenty-four hours later, co-registered intravascular 2D NIRF, X-ray angiography and intravascular ultrasound imaging were performed. In vivo EES-stented plaques contained substantially reduced NIRF inflammatory protease activity compared with untreated plaques and BMS-stented plaques (P = 0.006). Ex vivo macroscopic NIRF imaging of plaque protease activity corroborated the in vivo results (P = 0.003). Histopathology analyses revealed that EES-treated plaques showed reduced neointimal and medial arterial macrophage and cathepsin B expression compared with unstented and BMS-treated plaques.

Conclusions: EES-stenting stabilizes plaque inflammation as assessed by translational intravascular NIRF molecular imaging in vivo. These data further support that EES may provide a local approach for stabilizing inflamed plaques.

Keywords: atherosclerosis; everolimus; fluorescence imaging; inflammation; molecular imaging; stent.

MeSH terms

  • Animals
  • Coronary Artery Disease / diagnostic imaging*
  • Coronary Artery Disease / pathology
  • Coronary Artery Disease / therapy
  • Disease Models, Animal
  • Drug-Eluting Stents*
  • Everolimus / pharmacology*
  • Inflammation / diagnostic imaging*
  • Inflammation / pathology
  • Male
  • Molecular Imaging / methods
  • Plaque, Atherosclerotic / diagnostic imaging*
  • Plaque, Atherosclerotic / pathology
  • Rabbits
  • Random Allocation
  • Sensitivity and Specificity
  • Spectrometry, Fluorescence / methods
  • Spectroscopy, Near-Infrared / methods*

Substances

  • Everolimus