title: Low blood flow after angioplasty augments mechanisms of restenosis: inward vessel remodeling, cell migration, and activity of genes regulating migration.
abstract: -The predominant cause of restenosis after angioplasty is now thought to be inward remodeling, but the mechanisms responsible are unknown. Remodeling in normal vessels is regulated by the endothelium in response to altered shear stress. Although the endothelium is often damaged by angioplasty, restenosis rates after angioplasty have been correlated with impaired coronary flow. Thus, we examined how increases or decreases in blood flow through balloon catheter-injured rat carotid arteries affect vessel morphometry (4, 10, and 28 days), cell migration (4 days), and levels of promigratory mRNAs (2 and 10 days). After 28 days, the luminal area in vessels with low blood flow was significantly less than in those with normal and high blood flow (0.17+/-0.01 [low] versus 0.24+/-0.06 [normal] versus 0.30+/-0.02 [high] mm(2), P:<0.01), predominantly because of accentuated inward remodeling (or reduced area within the external elastic lamina; 0.42+/-0.02 [low] versus 0.54+/-0.07 [normal] versus 0.53+/-0.04 [high] mm(2), P:<0.05). Low flow also enhanced smooth muscle cell migration 4 days after injury by 90% above normal and high flows (P:<0.01). Two days after injury, low flow significantly increased levels of mRNAs encoding promigratory peptides (integrin alpha(v)ss(3), transforming growth factor-ss(1), CD44v6, MDC9, urokinase plasminogen activator receptor, and ss-inducible gene h3); these changes persisted 10 days after injury and were localized to the neointima. Low blood flow may promote restenosis after angioplasty because of its adverse effect on vessel remodeling, and it is associated with the augmented expression of multiple genes central to cell migration and restenosis.
authors.affiliation: Cell Biology Laboratory, Baker Medical Research Institute, and Alfred Baker Medical Unit, Alfred Hospital, Prahran, Victoria, Australia. mrward@doh.health.nsw.gov.au
authors.forename: M R
authors.initials: MR
authors.lastname: Ward
authors.forename: P S
authors.initials: PS
authors.lastname: Tsao
authors.forename: A
authors.initials: A
authors.lastname: Agrotis
authors.forename: R J
authors.initials: RJ
authors.lastname: Dilley
authors.forename: G L
authors.initials: GL
authors.lastname: Jennings
authors.forename: A
authors.initials: A
authors.lastname: Bobik
mesh_terms: D051722:ADAM Proteins; D000800:Angioplasty, Balloon / Q000009:adverse effects*; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D002339:Carotid Arteries / Q000503:physiopathology*; D020212:Carotid Artery Injuries / Q000209:etiology / Q000503:physiopathology*; D002465:Cell Movement; D003331:Coronary Vessels / Q000293:injuries; D019483:Disintegrins / Q000502:physiology; D004730:Endothelium, Vascular / Q000503:physiopathology; D006023:Glycoproteins / Q000502:physiology; D006083:Graft Occlusion, Vascular / Q000503:physiopathology*; D006439:Hemodynamics / Q000502:physiology*; D006801:Humans; D018960:Hyaluronan Receptors / Q000502:physiology; D008565:Membrane Proteins; D008666:Metalloendopeptidases / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D012333:RNA, Messenger / Q000502:physiology; D015291:Transforming Growth Factors / Q000502:physiology; D014568:Urokinase-Type Plasminogen Activator / Q000502:physiology
chemical_list: C112697:CD44v6 antigen; D019483:Disintegrins; D006023:Glycoproteins; D018960:Hyaluronan Receptors; D008565:Membrane Proteins; D012333:RNA, Messenger; D015291:Transforming Growth Factors; D014568:Urokinase-Type Plasminogen Activator; D051722:ADAM Proteins; C098339:ADAM9 protein, human; D008666:Metalloendopeptidases