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Simvastatin increases the activity of endothelial nitric oxide synthase via enhancing phosphorylation

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Summary

3-hydroxy-3-methylgulutaryl-coenzyme A (HMG-CoA) reductase inhibitors or statins are a kind of lipid-lowering agents and have been used for the prevention and treatment of cardiovascular diseases. Recent studies suggested that statins, besides lowering cholesterol, may protect vessels by enhancing the activity of endothelial nitric oxide synthase (eNOS). In the present study, we investigated if simvastatin increases eNOS activity through its phosphorylation in 293 cells (293-eNOS) with stable expression of eNOS. The results showed that incubation of 293-eNOS cells with simvastatin (10 μm/L) for 2 h significantly increased in the activity of eNOS as shown by the conversion of L-arginine to L-citrulline (2889.70±201.51 versus 5630.18±218.75 pmol/min · mg proteins) (P<0.01). Western blotting revealed that simvastatin increased phosphorylation of eNOS at 1177 (ser) and also 495 (thr) but did not affect the overall expression of eNOS or inducible NOS. Further study found that simvastatin raised phosphorylation levels of Akt and AMPK, and such effect could be antagonized by Akt inhibitor or AMPK inhibitor. These results suggest that simvastatin could stimulate the activity of eNOS via its phosphorylation by Akt and AMPK, which provides a new mechanism, other than lipid-lowering effect, for the cardiovascular protection of statins.

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Authors and Affiliations

  1. The Institute of Hypertension and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science, Wuhan, 430030, China

    Xiaoxia Li  (李小霞), Peihua Wang  (汪培华), Xizhen Xu  (徐西振), Yong Wang  (王 勇) & Daowen Wang  (汪道文)

  2. Davis Heart & Lung Research Institute, the Ohio State University Medical Center, Ohio, 43210, USA

    Yong Xia  (夏 永)

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  1. Xiaoxia Li  (李小霞)
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  2. Peihua Wang  (汪培华)
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  3. Xizhen Xu  (徐西振)
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  4. Yong Wang  (王 勇)
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  5. Yong Xia  (夏 永)
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  6. Daowen Wang  (汪道文)
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Additional information

Xiaoxia LI and Peihua WANG contributed equally to this work.

This project was supported by grants from National Natural Sciences Foundation of China (No. 30430320 and 30770882) and National 973 Project (No. 2007CB512004).

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Li, X., Wang, P., Xu, X. et al. Simvastatin increases the activity of endothelial nitric oxide synthase via enhancing phosphorylation. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 29, 286–290 (2009). https://doi.org/10.1007/s11596-009-0304-0

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  • DOI: https://doi.org/10.1007/s11596-009-0304-0

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