title: Iron and noncontrast magnetic resonance T2* as a marker of intraplaque iron in human atherosclerosis.
abstract: OBJECTIVE
  Iron has been implicated in atherogenesis and plaque destabilization, whereas less is known about iron-related proteins in this disease. We compared ex vivo quantities with in vivo vessel wall T2*, which is a noncontrast magnetic resonance relaxation time that quantitatively shortens with increased tissue iron content. We also tested the hypothesis that patients with carotid atherosclerosis have abnormal T2* times vs controls that would help support a role for iron in human atherosclerosis.
  
  
  METHODS
  Forty-six patients undergoing carotid endarterectomy and 14 subjects without carotid disease were prospectively enrolled to undergo carotid magnetic resonance imaging. Ex vivo measurements were performed on explanted plaque and 17 mammary artery samples.
  
  
  RESULTS
  Plaques vs normal arteries had higher levels of ferritin (median, 7.3 [interquartile range (IQR), 4-13.8] vs 1.0 [IQR, 0.6-1.3] ng/mg; P < .001) and oxidized low-density lipoprotein (median, 0.17 [IQR, 0.12-0.30] vs 0.01 [IQR, 0.003-0.03] ng/mg; P < .001) as well as hepcidin (median, 8.7 [IQR, 4.6-12.4] vs 2.6 [IQR, 1.3-7.0] ng/mL; P = .03); serum hepcidin levels did not distinguish atherosclerosis patients from controls (median, 40.6 [IQR, 18.8-88.6] vs 33.9 [IQR, 17.6-55.2]; P = .42). Shorter in vivo T2* paralleled larger plaque volume (ρ = -.44; P = .01), and diseased arteries had shorter T2* values compared with controls (median, 17.7 ± 4.3 vs 23.0 ± 2.4 ms; P < .001).
  
  
  CONCLUSIONS
  Diseased arteries have greater levels of iron-related proteins ex vivo and shorter T2* times in vivo. Further studies should help define the role of T2* as a biomarker of iron and atherosclerosis.
authors.affiliation: The Ohio State University, Davis Heart and Lung Research Institute, Columbus, Ohio.
authors.forename: Marshall W
authors.initials: MW
authors.lastname: Winner
authors.affiliation: The Ohio State University, Davis Heart and Lung Research Institute, Columbus, Ohio.
authors.forename: Travis
authors.initials: T
authors.lastname: Sharkey-Toppen
authors.affiliation: The Ohio State University, Davis Heart and Lung Research Institute, Columbus, Ohio.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The Ohio State University, Davis Heart and Lung Research Institute, Columbus, Ohio.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Pennell
authors.affiliation: The Ohio State University, Davis Heart and Lung Research Institute, Columbus, Ohio.
authors.forename: Orlando P
authors.initials: OP
authors.lastname: Simonetti
authors.affiliation: The Ohio State University, Davis Heart and Lung Research Institute, Columbus, Ohio.
authors.forename: Jay L
authors.initials: JL
authors.lastname: Zweier
authors.affiliation: The Ohio State University, Davis Heart and Lung Research Institute, Columbus, Ohio.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Vaccaro
authors.affiliation: The Ohio State University, Davis Heart and Lung Research Institute, Columbus, Ohio. Electronic address: raman.1@osu.edu.
authors.forename: Subha V
authors.initials: SV
authors.lastname: Raman
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000032:analysis; D002339:Carotid Arteries / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D002340:Carotid Artery Diseases / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D016022:Case-Control Studies; D016894:Endarterectomy, Carotid; D005260:Female; D005293:Ferritins / Q000032:analysis; D064451:Hepcidins / Q000032:analysis; D006801:Humans; D007501:Iron / Q000032:analysis*; D008077:Lipoproteins, LDL / Q000032:analysis; D018810:Magnetic Resonance Angiography; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic; D011237:Predictive Value of Tests; D011446:Prospective Studies
chemical_list: D015415:Biomarkers; D064451:Hepcidins; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D005293:Ferritins; D007501:Iron