title: Local Stent-Based Release of Transforming Growth Factor-β1 Limits Arterial In-Stent Restenosis.
abstract: The long-term success of intra-arterial stenting remains limited by in-stent restenosis (ISR). Transforming growth factor-β1 (TGF-β1) can inhibit smooth muscle cell (SMC) proliferation and migration and convert SMCs into extracellular matrix (ECM)-synthesizing cells. Here, we evaluate the effects of stent-based delivery of TGF-β1 on ISR in a rabbit model. Channeled stents loaded with TGF-β1 or control microspheres were deployed in rabbit aortas. Stented aortas were harvested at 7 and 28 d and evaluated for Ki-67-positive cells, collagenous ECM production, and intima-to-media (I/M) ratio. At 7 d, the TGF-β1 group exhibited fewer Ki-67-positive cells were found for the TGF-β1 group (17.87 ± 2.18 cells per mm(2)) relative to control (25.07 ± 2.65 cells per mm(2), p = 0.04), but increased collagen content (31.4 ± 2.5 percentage area) compared with control (29.3 ± 1.2 percentage area, p = 0.019). The I/M ratio in the TGF-β1 group was reduced by 50% and 9.1% versus control at 7 d (0.13 ± 0.02 vs. 0.26 ± 0.02, p = 0.0001) and 28 d (1.80 ± 0.05 vs. 1.98 ± 0.08, p = 0.0038), respectively. Stent-based controlled release of TGF-β1 limits ISR and is associated with inhibition of SMC proliferation but an increase in ECM production.
authors.affiliation: Division of Interventional Radiology, Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA davidwang@stanford.edu.
authors.forename: David S
authors.initials: DS
authors.lastname: Wang
authors.affiliation: Division of Interventional Radiology, Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Fumikiyo
authors.initials: F
authors.lastname: Ganaha
authors.affiliation: Division of Interventional Radiology, Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Edward Y
authors.initials: EY
authors.lastname: Kao
authors.affiliation: Division of Interventional Radiology, Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Lee
authors.affiliation: Division of Interventional Radiology, Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Elkins
authors.affiliation: Division of Interventional Radiology, Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Waugh
authors.affiliation: Division of Interventional Radiology, Department of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Dake
mesh_terms: D000818:Animals; D001024:Aortic Valve Stenosis / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D049109:Cell Proliferation; D003094:Collagen / Q000032:analysis; D004195:Disease Models, Animal; D054855:Drug-Eluting Stents; D005109:Extracellular Matrix / Q000737:chemistry; D019394:Ki-67 Antigen / Q000032:analysis; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D011817:Rabbits; D053773:Transforming Growth Factor beta1 / Q000008:administration & dosage*; D016896:Treatment Outcome; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology
chemical_list: D019394:Ki-67 Antigen; D053773:Transforming Growth Factor beta1; D003094:Collagen
keywords: extracellular matrix; rabbit; restenosis; smooth muscle cell; stent; transforming growth factor–β1