title: Everolimus-eluting stents stabilize plaque inflammation in vivo: assessment by intravascular fluorescence molecular imaging.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Cardiology Division, Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Simches Research Building Room 3206, 185 Cambridge Street, Boston, MA 02114, USA.|Department of Cardiology, Ronald Reagan Medical Center, University of California in Los Angeles, Los Angeles CA, USA.
authors.forename: Marcella A
authors.initials: MA
authors.lastname: Calfon Press
authors.affiliation: Cardiology Division, Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Simches Research Building Room 3206, 185 Cambridge Street, Boston, MA 02114, USA.|Department of Electrical and Computer Engineering, Northeastern University, Boston, MA, USA.
authors.forename: Georgios
authors.initials: G
authors.lastname: Mallas
authors.affiliation: Cardiology Division, Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Simches Research Building Room 3206, 185 Cambridge Street, Boston, MA 02114, USA.|Institute for Biological and Medical Imaging (IBMI), Helmholtz Center Munich & Technical University of Munich, Munich, Germany.
authors.forename: Amir
authors.initials: A
authors.lastname: Rosenthal
authors.affiliation: Cardiology Division, Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Simches Research Building Room 3206, 185 Cambridge Street, Boston, MA 02114, USA.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hara
authors.affiliation: Cardiology Division, Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Simches Research Building Room 3206, 185 Cambridge Street, Boston, MA 02114, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Mauskapf
authors.affiliation: Institute for Biological and Medical Imaging (IBMI), Helmholtz Center Munich & Technical University of Munich, Munich, Germany.
authors.forename: R Nika
authors.initials: RN
authors.lastname: Nudelman
authors.affiliation: Abbott Vascular Laboratories, Santa Clara, CA, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Sheehy
authors.affiliation: Abbott Vascular Laboratories, Santa Clara, CA, USA.
authors.forename: Igor V
authors.initials: IV
authors.lastname: Polyakov
authors.affiliation: CV Path Institute, Gaithersburg, MD, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Kolodgie
authors.affiliation: CV Path Institute, Gaithersburg, MD, USA.
authors.forename: Renu
authors.initials: R
authors.lastname: Virmani
authors.affiliation: Cardiology Division, Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Simches Research Building Room 3206, 185 Cambridge Street, Boston, MA 02114, USA.
authors.forename: J Luis
authors.initials: JL
authors.lastname: Guerrero
authors.affiliation: Institute for Biological and Medical Imaging (IBMI), Helmholtz Center Munich & Technical University of Munich, Munich, Germany.
authors.forename: Vasilis
authors.initials: V
authors.lastname: Ntziachristos
authors.affiliation: Cardiology Division, Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Simches Research Building Room 3206, 185 Cambridge Street, Boston, MA 02114, USA.|Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Farouc A
authors.initials: FA
authors.lastname: Jaffer
mesh_terms: D000818:Animals; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging* / Q000473:pathology / Q000628:therapy; D004195:Disease Models, Animal; D054855:Drug-Eluting Stents; D000068338:Everolimus / Q000494:pharmacology*; D007249:Inflammation / Q000000981:diagnostic imaging* / Q000473:pathology; D008297:Male; D057054:Molecular Imaging / Q000379:methods; D058226:Plaque, Atherosclerotic / Q000000981:diagnostic imaging* / Q000473:pathology; D011817:Rabbits; D011897:Random Allocation; D012680:Sensitivity and Specificity; D013050:Spectrometry, Fluorescence / Q000379:methods; D019265:Spectroscopy, Near-Infrared / Q000379:methods*
chemical_list: D000068338:Everolimus
keywords:  atherosclerosis; everolimus; fluorescence imaging; inflammation; molecular imaging; stent