| Overexpression of eNOS Improves Endothelium-Dependent Vasodilation in Arteries Infused with Helper-Dependent Adenovirus. | |
| | |
MedLine Citation:
|
PMID: 22906141 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Adenoviral vectors (Ad) are useful tools for in vivo gene transfer into endothelial cells. However, endothelium-dependent vasodilation is impaired after Ad infusion, and this impairment is not prevented by use of advanced-generation "helper-dependent" (HD) Ad that lack all viral genes. We hypothesized that endothelium-dependent vasodilation could be improved in Ad-infused arteries by overexpression of endothelial nitric oxide synthase (eNOS). We tested this hypothesis in hyperlipidemic, atherosclerosis-prone rabbits because HDAd will likely be used for treating and preventing atherosclerosis. Moreover, the consequences of eNOS overexpression might differ in normal and atherosclerosis-prone arteries and could include atherogenic effects, as reported in transgenic mice. We cloned rabbit eNOS and constructed an HDAd that expresses it. HDAdeNOS increased NO production by cultured endothelial cells and increased arterial eNOS mRNA in vivo by ~10-fold. Compared to arteries infused with a control HDAd, HDAdeNOS-infused arteries of hyperlipidemic rabbits had significantly improved endothelium-dependent vasodilation, and similar responses to phenylephrine and nitroprusside. Moreover, infusion of HDAdeNOS had local atheroprotective effects including large, significant decreases in intimal lipid accumulation and arterial TNF-α expression (P ≤ 0.04 for both). HDAdeNOS infusion yields a durable (≥ 2 weeks) increase in arterial eNOS expression, improves vasomotor function, and reduces artery wall inflammation and lipid accumulation. Addition of an eNOS expression cassette improves the performance of HDAd, has no harmful effects, and may reduce atherosclerotic lesion growth. |
| | |
Authors:
|
Bo Jiang; Liang Du; Rowan Flynn; Nagadhara Dronadula; Jingwan Zhang; Francis Kim; David A Dichek |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-8-20 |
Journal Detail:
|
Title: Human gene therapy Volume: - ISSN: 1557-7422 ISO Abbreviation: Hum. Gene Ther. Publication Date: 2012 Aug |
Date Detail:
|
Created Date: 2012-8-21 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9008950 Medline TA: Hum Gene Ther Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
University of Washington, Medicine/Cardiology, Seattle, Washington, United States; bjian1@gmail.com. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Efficacy of tuned waveforms based on different membrane time constants on defibrillation thresholds:...
Next Document: Anemia and the onset of gout in a population-based cohort of adults: Atherosclerosis Risk in Communi...