doi: 10.1161/01.CIR.0000050549.85811.9D
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(Circulation. 2003;107:e25.)
© 2003 American Heart Association, Inc.
Correspondence |
Simvastatin Reduces Neointimal Thickening After Experimental Angioplasty
Division of Cardiology, Magna Graecia University, Catanzaro, Italy
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.
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.
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.
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