title: Low levels of Nogo-B in human carotid atherosclerotic plaques are associated with an atheromatous phenotype, restenosis, and stenosis severity.
abstract: OBJECTIVE
  Reticulon-4/Nogo (Nogo-B) protects mouse arteries from lumen loss by reducing smooth muscle cell (SMC) migration and intimal thickening. Our goal was to determine plaque and circulating levels of Nogo-B in atherosclerotic and control subjects. Therefore, we studied the relationships between local Nogo-B, plaque characteristics, and clinical data in patients undergoing carotid endarterectomy.
  
  
  RESULTS
  Western blot analysis showed that endarterectomy specimens from the femoral (n=19) and carotid arteries (n=145) contained significantly less Nogo-B than nonatherosclerotic mammary arteries (n=8; P<0.003) and aortas (n=15; P=0.03). Immunohistochemistry revealed that in atherosclerotic lesions, Nogo-B was expressed by macrophage/foam cells, SMC rich, and neo-vascularized areas. Atheromatous plaques (>40% fat content) showed a significant reduction in Nogo-B expression (P=0.002). Nogo-B expression levels were significantly lower in patients with more than 90% of carotid stenosis (P=0.04) or restenotic lesions after prior carotid intervention (duplex; P=0.01). In contrast, plasmatic levels of Nogo-B (soluble Nogo-B) did not differ between atherosclerotic subjects (n=68) and risk-factor matched controls (n=63; P=0.5).
  
  
  CONCLUSIONS
  Our findings suggest that local reduction of Nogo-B in atherosclerotic tissue might contribute to plaque formation and/or instability triggering luminal narrowing. In contrast, plasma Nogo-B levels are not associated with clinically manifested atherosclerotic disease.
authors.affiliation: Department of Cardiology, Experimental Cardiology Laboratory, University Medical Center, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Rodriguez-Feo
authors.forename: Willem E
authors.initials: WE
authors.lastname: Hellings
authors.forename: Bart A N
authors.initials: BA
authors.lastname: Verhoeven
authors.forename: Frans L
authors.initials: FL
authors.lastname: Moll
authors.forename: Dominique P V
authors.initials: DP
authors.lastname: de Kleijn
authors.forename: Jay
authors.initials: J
authors.lastname: Prendergast
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.forename: Yolanda
authors.initials: Y
authors.lastname: van der Graaf
authors.forename: George
authors.initials: G
authors.lastname: Tellides
authors.forename: William C
authors.initials: WC
authors.lastname: Sessa
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
mesh_terms: D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D015153:Blotting, Western; D002342:Carotid Artery, External / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D002343:Carotid Artery, Internal / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D016893:Carotid Stenosis / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D016022:Case-Control Studies; D015536:Down-Regulation; D016894:Endarterectomy, Carotid; D005260:Female; D005263:Femoral Artery / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis* / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000032:analysis* / Q000097:blood; D008875:Middle Aged; D009185:Myelin Proteins / Q000032:analysis* / Q000097:blood; D000070798:Nogo Proteins; D010641:Phenotype; D012008:Recurrence; D012107:Research Design; D012720:Severity of Illness Index
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603199:RTN4 protein, human; C000603201:Rtn4 protein, mouse