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

source: © 2016 European Heart Journal

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.
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.[Read more…]

FRI of plaque

Fig. Ex vivo FRI analyses of plaque inflammatory cysteine protease activity in BMS-, EES-treated, and unstented plaque zones. (A–C) Ex vivo FRI alignments from three representative animals. All NIRF images were obtained with a one second exposure. Image windows optimized for individual images.

Marcella A. Calfon Press, Georgios Mallas, Amir Rosenthal, Tetsuya Hara, Adam Mauskapf, R. Nika Nudelman, Alexander Sheehy, Igor V. Polyakov, Frank Kolodgie, Renu Virmani, J. Luis Guerrero, Vasilis Ntziachristos, Farouc A. Jaffer.European Heart Journal – Cardiovascular Imaging, Volume 18, Issue 5, 1 May 2017, Pages 510–518.