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

<span class="paragraphSection"><div class="boxTitle">Aims</div>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 <span style="font-style:italic;">in vivo</span>. Here, we investigate whether everolimus-eluting stents (EES) can locally suppress plaque inflammatory protease activity <span style="font-style:italic;">in vivo</span> using intravascular near-infrared fluorescence (NIRF) molecular imaging.<div class="boxTitle">Methods and results</div>Balloon-injured, hyperlipidaemic rabbits with atherosclerosis received non-overlapping EES and bare metal stents (BMS) placement into the infrarenal aorta (<span style="font-style:italic;">n</span> = 7 EES, <span style="font-style:italic;">n</span> = 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. <span style="font-style:italic;">In vivo</span> EES-stented plaques contained substantially reduced NIRF inflammatory protease activity compared with untreated plaques and BMS-stented plaques (<span style="font-style:italic;">P</span> = 0.006). <span style="font-style:italic;">Ex vivo</span> macroscopic NIRF imaging of plaque protease activity corroborated the <span style="font-style:italic;">in vivo</span> results (<span style="font-style:italic;">P</span> = 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.<div class="boxTitle">Conclusions</div>EES-stenting stabilizes plaque inflammation as assessed by translational intravascular NIRF molecular imaging <span style="font-style:italic;">in vivo</span>. These data further support that EES may provide a local approach for stabilizing inflamed plaques.</span>

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