Local delivery of c-myb antisense oligonucleotides during balloon angioplasty

• Published in: Catheterization and cardiovascular diagnosis 1997-07, Vol.41 (3), p.232-240
• Main Authors: Azrin, Michael A., Mitchel, Joseph F., Bow, Laurine M., Pedersen, Carl A., Cartun, Richard W., Aretz, Thomas H., Waters, David D., McKay, Raymond G.
• Format: Article
• Language: English
• Subjects: Angioplasty, Balloon, Coronary - instrumentation; Animals; antisense; Autoradiography; balloon angioplasty; Biological and medical sciences; Cell Division - drug effects; Coronary Disease - drug therapy; Coronary Disease - pathology; Coronary Vessels - drug effects; Coronary Vessels - pathology; Diseases of the cardiovascular system; drug delivery; Drug Delivery Systems - instrumentation; Feasibility Studies; Female; Lymphocyte Activation - drug effects; Medical sciences; Mice; Microscopy, Fluorescence; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - pathology; Oligonucleotides, Antisense - administration & dosage; Oligonucleotides, Antisense - pharmacokinetics; oncogene; Proliferating Cell Nuclear Antigen - metabolism; Proto-Oncogene Proteins - antagonists & inhibitors; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-myb; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); restenosis; Swine; Trans-Activators - antagonists & inhibitors; Trans-Activators - metabolism
• ISSN: 0098-6569; 1097-0304
• DOI: 10.1002/(SICI)1097-0304(199707)41:3<232::AID-CCD2>3.0.CO;2-7

Intraluminal delivery of antisense oligonucleotides to c‐myb was assessed following balloon angioplasty in swine peripheral arteries. Successful delivery and intramural persistence of oligonucleotide for over 24 h were demonstrated following angioplasty with hydrogel balloons coated with 32P‐labeled antisense. Delivery of fluorescein‐labeled antisense demonstrated further localization within the arterial media and intracellularly. Preliminary in vitro studies demonstrated the feasibility of inhibition of porcine lymphocyte proliferation using the murine antisense to c‐myb. Twelve iliac or carotid arteries underwent angioplasty with antisense‐coated balloons, while the contralateral vessels underwent angioplasty with the same‐sized balloons coated with the complementary sense strand. Six to seven days later, dilated arterial segments were surgically isolated. In 10 of 12 vessel pairs, antisense‐treated vessels demonstrated less cellular proliferation than did contralateral sense‐treated vessels, as assessed by quantitative immunohistochemical staining of proliferating cell nuclear antigen, and smooth muscle cell proliferation was reduced 18% in antisense‐treated vessels compared to the contralateral sense‐treated vessels (PCNA‐positive nuclear area: 7.7 ± 4.9% vs. 9.3 ± 5.2%, P < 0.04). Intraluminal delivery of antisense oligonucleotides to c‐myb is feasible with a catheter‐based system and may reduce smooth muscle cell proliferation following arterial injury. Cathet. Cardiovasc. Diagn. 41:232–240, 1997. © 1997 Wiley‐Liss, Inc.