The statins reduce cholesterol synthesis through inhibition of HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase and are widely prescribed for hyperlipidaemia to reduce the risk of atherosclerotic complications. The beneficial effect of lipid lowering by statins in the treatment of coronary heart disease has been demonstrated in large clinical trials. However, statins appear to have additional benefits on vascular function above and beyond their lipid lowering effects. Through inhibition of L-mevalonate synthesis, statins also prevent the synthesis of isoprenoid intermediates, including farnesylpyrophosphate and geranylgeranylpyrophosphate. Isoprenylation is important in the post-translational modification of a variety of proteins, including the small GTPases Rho, Rac and Ras, and hence plays an integral role in cellular signalling. Moreover, interference with isoprenylation underlies many of the beneficial actions of the statins on vascular endothelium, which include increased endothelial nitric oxide synthase expression, pro-angiogenic effects, increased fibrinolytic activity, immunomodulatory and anti-inflammatory actions, including increased resistance to complement. This has led to interest in the use of this class of drugs outside the realm of cardiovascular disease.
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September 2003
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Review Article|
September 01 2003
Statins and their role in vascular protection
Justin C. MASON
1British Heart Foundation Cardiovascular Medicine Unit, National Heart and Lung Institute, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 ONN, U.K.
Correspondence: Dr Justin Mason (e-mail [email protected]).
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Publisher: Portland Press Ltd
Received:
April 23 2003
Revision Received:
May 28 2003
Accepted:
June 06 2003
Accepted Manuscript online:
June 06 2003
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2003 The Biochemical Society
2003
Clin Sci (Lond) (2003) 105 (3): 251–266.
Article history
Received:
April 23 2003
Revision Received:
May 28 2003
Accepted:
June 06 2003
Accepted Manuscript online:
June 06 2003
Citation
Justin C. MASON; Statins and their role in vascular protection. Clin Sci (Lond) 1 September 2003; 105 (3): 251–266. doi: https://doi.org/10.1042/CS20030148
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