title: Evidence supporting changes in Nogo-B levels as a marker of neointimal expansion but not adaptive arterial remodeling.
abstract: Both neointimal hyperplasia and inward remodeling contribute to restenosis and lumen loss. Nogo-B has been recently described as an inhibitor of vascular injury and neointimal hyperplasia. To determine whether Nogo-B expression may be a mediator of inward remodeling, we examine the localization of expression of Nogo-B in an in vivo model that examines both neointimal hyperplasia and inward remodeling. The rabbit carotid artery was subjected to balloon injury, outflow branch ligation to reduce flow, or both balloon injury and reduction in flow. In balloon injury-induced neointimal hyperplasia Nogo-B expression was reduced in the intima and media but stimulated in the adventitia. In low flow-induced inward remodeling medial Nogo-B expression was not reduced and adventitial Nogo-B expression was not stimulated. Low flow significantly augmented balloon injury-induced neointimal hyperplasia and was accompanied by reduced intimal and medial Nogo-B expression, and increased adventitial Nogo-B expression in both smooth muscle cells and macrophages. Low flow-induced inward remodeling is not associated with changes in medial Nogo-B expression and is distinct from injury-induced neointimal hyperplasia. Pharmacological strategies to inhibit neointimal hyperplasia and restenosis using normal flow models may only partially account for lumen loss and therefore may not accurately predict responses in patients with extensive outflow disease.
authors.affiliation: Department of Surgery, Yale University School of Medicine, New Haven, CT 06519, United States.
authors.forename: Jacek J
authors.initials: JJ
authors.lastname: Paszkowiak
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Maloney
authors.forename: Fabio A
authors.initials: FA
authors.lastname: Kudo
authors.forename: Akihito
authors.initials: A
authors.lastname: Muto
authors.forename: Desarom
authors.initials: D
authors.lastname: Teso
authors.forename: Reuben C
authors.initials: RC
authors.lastname: Rutland
authors.forename: Tormod S
authors.initials: TS
authors.lastname: Westvik
authors.forename: Jose M
authors.initials: JM
authors.lastname: Pimiento
authors.forename: George
authors.initials: G
authors.lastname: Tellides
authors.forename: William C
authors.initials: WC
authors.lastname: Sessa
authors.forename: Alan
authors.initials: A
authors.lastname: Dardik
mesh_terms: D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000032:analysis; D001783:Blood Flow Velocity; D002339:Carotid Arteries / Q000737:chemistry / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery; D016893:Carotid Stenosis / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D002404:Catheterization; D049109:Cell Proliferation; D003238:Connective Tissue / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D006965:Hyperplasia; D008026:Ligation; D008297:Male; D009185:Myelin Proteins / Q000032:analysis*; D000070798:Nogo Proteins; D011817:Rabbits; D013314:Stress, Mechanical; D013718:Tensile Strength; D017539:Tunica Intima / Q000737:chemistry / Q000473:pathology*; D017540:Tunica Media / Q000737:chemistry / Q000473:pathology*
chemical_list: D015415:Biomarkers; D009185:Myelin Proteins; D000070798:Nogo Proteins