Rheumatology Advance Access originally published online on January 28, 2008
Rheumatology 2008 47(3):381-382; doi:10.1093/rheumatology/kem381
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Comment on: Atorvastatin therapy improves endothelial-dependent vasodilation in patients with systemic lupus erythematosus: an 8 week controlled trial
Academic Unit of Musculoskeletal Disease, Chapel Allerton Hospital. Chapeltown Road, Leeds LS7 4SA, UK
Correspondence to: P. J. Kotyla, Academic Unit of Musculoskeletal Disease, Chapel Allerton Hospital. Chapeltown Road, Leeds LS7 4SA, UK. E-mail: pkotyla{at}slam.katowice.pl
SIR, I have read with the interest the paper by Dr Ferreira and colleagues [1] regarding the therapeutic potential of atorvastatin in restoration of impaired endothelial function in patients with SLE. As the authors pointed out in their paper, premature atherosclerosis in patients with SLE is recognized nowadays as the main challenge. The problem, although well-known since the late 1970s, had not been explained satisfactorily. From the 1990s atherosclerosis has been recognized as a form of inflammation that explains why inflammatory states (mainly autoimmune disorders including inflammatory connective tissue diseases) may predispose to the early development of atherosclerosis. At the same time, progress in non-invasive vascular techniques has been achieved resulting in introduction of methods that give an excellent insight into the function of the endothelium [e.g. flow-mediated dilatation (FMD)].
Statins, the 3-hydroxy-3methyl-glutaryl Coenzyme A inhibitors, have proven their efficacy in primary and secondary prevention of vascular events. It was believed that it was realized mainly by suppression of a cholesterol synthesis. Recently, novel properties of statins other that their cholesterol-lowering activity have been discovered [2, 3]. These properties are called pleiotropic action and include direct influence of statins on endothelium, plaque formation, thromboxan synthesis as well as direct and indirect immunomodulatory activities [4].
The authors surprisingly observed reduction of SLE activity measured in SLEDAI scale. To support this observation I would like to underline that quite recently we observed similar reduction of SLEDAI in the group of female patients treated with another statin—simvastatin. Reduction of SLEDAI goes together with prominent suppression of TNF-
concentration in sera of patients treated. This phenomenon was observed just after 4 weeks of treatment with simvastatin at a dose of 20 mg [5]. In an unpublished part of this study, we also observed improvement of endothelial function with significantly increased FMD after the end of the study (3.4% vs 5.6%). This may lead to the thesis that restoration of endothelial function is not restricted to the single compound (atorvaststin) but may be recognized as a class of drug effect. Since TNF- is believed to mediate endothelial damage, it may also be speculated that suppression of TNF- levels after statin therapy might be one mechanism via which restoration of endothelial functions occurs.
Of special importance is also the fact that treatment of statins gives us unique possibility to prevent atherosclerosis, restore endothelial function but also via their immunomodulatory properties decrease activity of disease.
Disclosure statement: The author has declared no conflicts of interest.
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- Ferreira GA, Navarro TP, Telles RW, Andrade LEC, Sato I. Atorvastatin therapy improves endothelial-dependent vasodilatation in patients with systemic lupus erythematosus: an 8 weeks controlled trial. Rheumatology (2007) 46:1560–5.
[Abstract/Free Full Text] - Pierre-Paul D, Gathan V. Noncholesterol-lowering effects of statins. Vasc Endovasc Surg (2003) 37:301–13.[CrossRef]
- Sparrow CP, Burton CA, Hernandez M, et al. Simvastatin has anti-inflammatory and antiatherosclerotic activities independent of plasma cholesterol lowering. Arterioscl Thromb Vas Biol (2001) 21:115–21.
- Kotyla P, Sliwinska-Kotyla B. Therapeutic potential of HMG-CoA reductase inhibitors (statins) in systemic lupus erythematosus In: Steward TI, ed. Progress in systemic lupus erythematosus research. Nova Science Publishers (2007) In press.
- Kotyla PJ, Sliwinska-Kotyla B, Kucharz EJ. TNF alpha as a potential target in the treatment of SLE: a role of HMG-CoA reductase inhibitor simvastatin. J Rheumatol (2006) 33:2361.
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