Local delivery of c-myb antisense oligonucleotides during balloon angioplasty.
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.
Azrin
M A
MA
Department of Internal Medicine and Cardiology, Hartford Hospital, Connecticut, USA.
Mitchel
J F
JF
Bow
L M
LM
Pedersen
C A
CA
Cartun
R W
RW
Aretz
T H
TH
Waters
D D
DD
McKay
R G
RG
D015906:Angioplasty, Balloon, Coronary / Q000295:instrumentation*; D000818:Animals; D001345:Autoradiography; D002455:Cell Division / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy* / Q000473:pathology; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology; D016503:Drug Delivery Systems / Q000295:instrumentation*; D005240:Feasibility Studies; D005260:Female; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008856:Microscopy, Fluorescence; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020598:Proto-Oncogene Proteins c-myb; D013552:Swine; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000378:metabolism
D016376:Oligonucleotides, Antisense; D018809:Proliferating Cell Nuclear Antigen; D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D015534:Trans-Activators