Increased arginase II activity contributes to endothelial dysfunction through endothelial nitric oxide synthase uncoupling in aged mice |
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| Authors: | Woosung Shin Dan E. Berkowitz Sungwoo Ryoo |
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| Affiliation: | 1Department of Biology, College of Natural Sciences, Kangwon National University, Chuncheon 200-701, Korea.;2Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA.;3Department of Biomedical Engineering, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA. |
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| Abstract: | The incidence of cardiovascular disease is predicted to increase as the population ages. There is accumulating evidence that arginase upregulation is associated with impaired endothelial function. Here, we demonstrate that arginase II (ArgII) is upregulated in aortic vessels of aged mice and contributes to decreased nitric oxide (NO) generation and increased reactive oxygen species (ROS) production via endothelial nitric oxide synthase (eNOS) uncoupling. Inhibiting ArgII with small interfering RNA technique restored eNOS coupling to that observed in young mice and increased NO generation and decreased ROS production. Furthermore, enhanced vasoconstrictor responses to U46619 and attenuated vasorelaxation responses to acetylcholine in aged vasculature were markedly improved following siRNA treatment against ArgII. These results might be associated with increased L-arginine bioavailability. Collectively, these results suggest that ArgII may be a valuable target in age-dependent vascular diseases. |
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| Keywords: | aging arginase II endothelial nitric oxide synthase uncoupling small interfering RNA vascular diseases |
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