title: A Microscopic and Biomarker Evaluation of Embolic Filter Debris Collected During Carotid Artery Stenting.
abstract: OBJECTIVE
  To evaluate and characterize debris retrieved from the cerebral embolic protection devices (EPDs) used during carotid artery stenting (CAS) and compare debris size, volume, tissue types, cellular composition, and protein biomarker expression in symptomatic and asymptomatic patients.
  
  
  METHODS
  Distal protection filters were retrieved from 22 consecutive patients (mean age 71.6 years, range 52-85; 16 men) undergoing elective CAS between July 2012 and February 2014 for >70% internal carotid artery stenosis (mean 85.4% ± 10.3%). Six patients were symptomatic. The debris within each EPD was visually characterized using stereomicroscopy and then processed for histology and immunohistochemistry. Biomarkers were immunohistochemically measured to evaluate plaque stability [matrix metalloproteinase-9 (MMP-9)], inflammation [glycoprotein CD68 and interleukin-6 (IL-6)], or phenotype [smooth muscle (SM)-actin and type IV collagen]. The immunohistochemical results were measured using semiquantitative grading criteria based on both staining intensity and distribution in the samples.
  
  
  RESULTS
  Macroscopic debris was visible in 5/22 EPDs; 3 of the 5 filters came from symptomatic patients. Microscopic debris was detected in all filters and ranged in size from 0.01 to 8.57 mm(2). Debris consisted of calcified, fibrous, and necrotic tissue, as well as fibrin and foam cells with no significant difference between the symptomatic and asymptomatic groups. There was no association between the degree or type of embolic material and stenosis severity, carotid tortuosity, calcium grade, soft plaque, or arch type. Symptomatic patients had a larger volume of debris (8.24 vs 0.58 mm(3), p<0.01), mean particle size (1.30 vs 0.32 mm(2), p<0.001), and expression of biomarkers IL-6 (2.17 vs 0.81, p<0.05), CD68 (2.00 vs 0.38, p<0.01), SM-actin (1.00 vs 0.25, p=0.055), type IV collagen (1.17 vs 0.25,p=0.082), and MMP-9 (1.00 vs 0.06, p<0.05).
  
  
  CONCLUSIONS
  Histological analysis revealed particulate embolization in all EPDs used during CAS. Symptomatic patients had a larger volume of embolic debris, mean particle size, and the biomarkers associated with inflammation, necrotic core, and diminished fibrous cap.
authors.affiliation: Department of Surgery, Prince of Wales Hospital, Sydney, Australia Surgical and Orthopaedic Research Laboratories, Prince of Wales Clinical School, Faculty of Medicine, Sydney, Australia The University of Sydney, Australia Faculty of Medicine, University of New South Wales, Sydney, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Surgery, Prince of Wales Hospital, Sydney, Australia Surgical and Orthopaedic Research Laboratories, Prince of Wales Clinical School, Faculty of Medicine, Sydney, Australia Faculty of Medicine, University of New South Wales, Sydney, Australia.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Surgery, Prince of Wales Hospital, Sydney, Australia Surgical and Orthopaedic Research Laboratories, Prince of Wales Clinical School, Faculty of Medicine, Sydney, Australia Faculty of Medicine, University of New South Wales, Sydney, Australia.
authors.forename: William R
authors.initials: WR
authors.lastname: Walsh
authors.affiliation: Department of Surgery, Prince of Wales Hospital, Sydney, Australia Faculty of Medicine, University of New South Wales, Sydney, Australia Adult Cancer Program, Lowy Cancer Research Centre, Faculty of Medicine, University of New South Wales, Sydney, Australia.
authors.forename: Jia-Lin
authors.initials: JL
authors.lastname: Yang
authors.affiliation: Faculty of Medicine, University of New South Wales, Sydney, Australia.
authors.forename: Luke
authors.initials: L
authors.lastname: Baker
authors.affiliation: Department of Surgery, Prince of Wales Hospital, Sydney, Australia The Vascular Institute, Prince of Wales, Sydney, Australia.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Lennox
authors.affiliation: Department of Surgery, Prince of Wales Hospital, Sydney, Australia Surgical and Orthopaedic Research Laboratories, Prince of Wales Clinical School, Faculty of Medicine, Sydney, Australia Faculty of Medicine, University of New South Wales, Sydney, Australia.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Crowe
authors.affiliation: Department of Surgery, Prince of Wales Hospital, Sydney, Australia Surgical and Orthopaedic Research Laboratories, Prince of Wales Clinical School, Faculty of Medicine, Sydney, Australia Faculty of Medicine, University of New South Wales, Sydney, Australia The Vascular Institute, Prince of Wales, Sydney, Australia r.varcoe@unsw.edu.au.
authors.forename: Ramon L
authors.initials: RL
authors.lastname: Varcoe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D002343:Carotid Artery, Internal / Q000737:chemistry* / Q000000981:diagnostic imaging / Q000473:pathology*; D016893:Carotid Stenosis / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D000072226:Computed Tomography Angiography; D057505:Embolic Protection Devices; D057510:Endovascular Procedures / Q000009:adverse effects / Q000295:instrumentation*; D005260:Female; D005355:Fibrosis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008853:Microscopy / Q000379:methods*; D008875:Middle Aged; D009336:Necrosis; D058226:Plaque, Atherosclerotic; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012720:Severity of Illness Index; D015607:Stents; D016896:Treatment Outcome; D018616:Ultrasonography, Doppler, Duplex
chemical_list: D015415:Biomarkers
keywords: angioplasty; atherosclerosis; biomarkers; carotid artery; carotid artery stenting; embolic protection device; filter; histology; immunohistochemistry; interleukin-6; matrix metalloproteinase-9; plaque; smooth muscle actin; stent