Inactivity of nitric oxide synthase gene in the atherosclerotic human carotid artery

Tanner, Felix C; van der Loo, Bernd; Shaw, Sidney; Greutert, Helen; Bachschmid, Markus M; Berrozpe, Maria; Rozenberg, Izabela; Blau, Nenad; Siebenmann, Robert; Schmidli, Jürg; Meyer, Peter; Lüscher, Thomas F (2007). Inactivity of nitric oxide synthase gene in the atherosclerotic human carotid artery. Basic research in cardiology, 102(4), pp. 308-317. Heidelberg: Springer-Medizin-Verlag 10.1007/s00395-007-0650-7

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OBJECTIVE: Nitric oxide (NO) inhibits thrombus formation, vascular contraction, and smooth muscle cell proliferation. We investigated whether NO release is enhanced after endothelial NO synthase (eNOS) gene transfer in atherosclerotic human carotid artery ex vivo. METHODS AND RESULTS: Western blotting and immunohistochemistry revealed that transduction enhanced eNOS expression; however, neither nitrite production nor NO release measured by porphyrinic microsensor was altered. In contrast, transduction enhanced NO production in non-atherosclerotic rat aorta and human internal mammary artery. In transduced carotid artery, calcium-dependent eNOS activity was minimal and did not differ from control conditions. Vascular tetrahydrobiopterin concentrations did not differ between the experimental groups.Treatment of transduced carotid artery with FAD, FMN, NADPH, L-arginine, and either sepiapterin or tetrahydrobiopterin did not alter NO release. Superoxide formation was similar in transduced carotid artery and control. Treatment of transduced carotid artery with superoxide dismutase (SOD), PEG-SOD, PEG-catalase did not affect NO release. CONCLUSIONS: eNOS transduction in atherosclerotic human carotid artery results in high expression without any measurable activity of the recombinant protein. The defect in the atherosclerotic vessels is neither caused by cofactor deficiency nor enhanced NO breakdown. Since angioplasty is performed in atherosclerotic arteries,eNOS gene therapy is unlikely to provide clinical benefit.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Unit Tiefenau Hospital [discontinued] > Forschungsgruppe Vasoaktive Peptide [discontinued]
04 Faculty of Medicine > Department of Cardiovascular Disorders (DHGE) > Clinic of Cardiovascular Surgery

UniBE Contributor:

Shaw, Sidney and Schmidli, Jürg

ISSN:

0300-8428

ISBN:

17356797

Publisher:

Springer-Medizin-Verlag

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:56

Last Modified:

25 May 2020 14:36

Publisher DOI:

10.1007/s00395-007-0650-7

PubMed ID:

17356797

Web of Science ID:

000247172400003

BORIS DOI:

10.7892/boris.23970

URI:

https://boris.unibe.ch/id/eprint/23970 (FactScience: 45468)

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