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(Circulation. 2003;107:e25.)
© 2003 American Heart Association, Inc.

Correspondence

Simvastatin Reduces Neointimal Thickening After Experimental Angioplasty

Ciro Indolfi, MD; Antonio Curcio, MD

Division of Cardiology, Magna Graecia University, Catanzaro, Italy

Massimo Chiariello, MD

Division of Cardiology, Frederico II University, Naples, Italy

To the Editor:

We read with interest the study by Chen and associates that showed that simvastatin reduces neointimal proliferation in mice after vascular injury in a cholesterol-independent manner.¹ However, we already documented this finding in vitro and in vivo in a previous article.²

In fact, it has been documented that simvastatin inhibits in vitro smooth muscle cell proliferation independent of cholesterol.² In addition, in vivo experiments have shown that statins potently affect neointimal proliferation in a dose-dependent manner in a reliable model of balloon injury in the rat.² This effect was abolished by local administration of mevalonate.² We are delighted that the study of Chen et al confirms,¹ in genetically modified mice, our findings.²

With regard to the potential mechanism of statin on neointimal proliferation, we previously discussed a key role of ras pathway in neointimal proliferation after balloon injury.³ Recently, we also showed that statins powerfully inhibit ras farnesilation and activation.⁴ Therefore, statin-induced Ras-MAPKKs pathway inhibition may play a critical role in the effect of simvastatin on neointimal formation after vascular injury.

References

1. Chen Z, Fukutomi T, Zago AC, et al. Simvastatin reduces neointimal thickening in low-density lipoprotein receptor-deficient mice after experimental angioplasty without changing plasma lipids. Circulation. 2002; 106: 20–23.[Abstract/Free Full Text]

2. Indolfi C, Cioppa A, Stabile E, et al. Effects of hydroxymethylglutaryl coenzyme A reductase inhibitor simvastatin on smooth muscle cell proliferation in vitro and neointimal formation in vivo after vascular injury. J Am Coll Cardiol. 2000; 35: 214–221.[Abstract/Free Full Text]

3. Indolfi C, Avvedimento EV, Rapacciuolo A, et al. Inhibition of cellular RAS prevents smooth muscle cell proliferation after vascular injury in vivo. Nat Med. 1995; 1: 541–545.[CrossRef][Medline] [Order article via Infotrieve]

4. Indolfi C, Di Lorenzo E, Perrino C, et al. Hydroxymethylglutaryl Coenzyme A reductase inhibitor simvastatin prevents cardiac hypertrophy induced by pressure-overload and inhibits p21ras activation. Circulation. 2002; 106: 2118–2124.[Abstract/Free Full Text]

This Article Extract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Indolfi, C. Articles by Chiariello, M. Search for Related Content PubMed PubMed Citation Articles by Indolfi, C. Articles by Chiariello, M. Related Collections Restenosis Cardiovascular Pharmacology Restenosis Cell signalling/signal transduction Smooth muscle proliferation and differentiation