Abstract | OBJECTIVES: BACKGROUND: Reduced local bioavailability and adverse side effects limit systemic administration of NO to modulate vascular response to injury. METHODS: RESULTS: Treatment with SPER/NO reduced the intimal area (0.011 +/- 0.009 vs. 0.035 +/- 0.006 mm2 control, p < 0.01) and the intima to media ratio (0.089 +/- 0.062 vs. 0.330 +/- 0.057 control, p < 0.005). Spermine/nitric oxide produced a profound inhibition of PCNA-positive cells (>75%, p < 0.005) and significantly suppressed the injury-induced activation of NF-kappaB. Vascular cyclic guanosine monophosphate (cGMP) levels were elevated after treatment with the SPER/NO (0.28 +/- 0.03 vs. 0.17 +/- 0.02 pmol/mg tissue control, p < 0.01). The inhibitory effects on neointimal proliferation were localized to the site of application of SPER/NO and were not associated with any changes in platelet aggregation or bleeding time. Neither SPER nor polymer alone had any significant effects on any of the variables examined. CONCLUSIONS: Polymeric-based perivascular delivery of a NO donor produces a marked localized inhibition of neointimal proliferation in balloon-injured arteries. This phenomenon is associated with suppression of NF-kappaB activation and elevation of the vascular cGMP at the site of injury.
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Authors | S Kaul, B Cercek, J Rengstrom, X P Xu, M D Molloy, P Dimayuga, A K Parikh, M C Fishbein, J Nilsson, T B Rajavashisth, P K Shah |
Journal | Journal of the American College of Cardiology
(J Am Coll Cardiol)
Vol. 35
Issue 2
Pg. 493-501
(Feb 2000)
ISSN: 0735-1097 [Print] United States |
PMID | 10676700
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- NF-kappa B
- Polymers
- Proliferating Cell Nuclear Antigen
- Polylactic Acid-Polyglycolic Acid Copolymer
- Polyglycolic Acid
- Spermine
- Nitric Oxide
- Lactic Acid
- Cyclic GMP
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Topics |
- Angioplasty, Balloon
(adverse effects)
- Animals
- Arteries
(drug effects, injuries, pathology)
- Bleeding Time
- Cell Division
(drug effects)
- Cyclic GMP
(metabolism)
- Drug Delivery Systems
- Hyperplasia
(metabolism, pathology, prevention & control)
- Lactic Acid
- Male
- NF-kappa B
(metabolism)
- Nitric Oxide
(metabolism)
- Platelet Aggregation
- Polyglycolic Acid
- Polylactic Acid-Polyglycolic Acid Copolymer
- Polymers
- Proliferating Cell Nuclear Antigen
(metabolism)
- Rats
- Rats, Sprague-Dawley
- Spermine
(administration & dosage)
- Tunica Intima
(drug effects, injuries, pathology)
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