Original ArticleEffect of Statins on the Viability of Macrophages and Smooth Muscle CellsCroons, Valerie PharmD, PhD*; De Meyer, Inge PharmD*; Houten, Sander M PhD†; Martinet, Wim PhD*; Bult, Hidde PhD*; Herman, Arnold G MD, PhD*; De Meyer, Guido R Y PharmD, PhD*Author Information From the *Division of Pharmacology, University of Antwerp, Antwerp, Belgium; and †Laboratory Genetic Metabolic Diseases, Academic Medical Center, Amsterdam, The Netherlands. Received for publication July 23, 2009; accepted December 14, 2009. Conflict of interest: The authors declare that they have no conflicts of interest to disclose. Reprints: Valerie Croons, PharmD, PhD, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium (e-mail: [email protected]). Journal of Cardiovascular Pharmacology: March 2010 - Volume 55 - Issue 3 - p 269-275 doi: 10.1097/FJC.0b013e3181d0bec3 Buy Metrics Abstract Because macrophages play an important role in the destabilization of atherosclerotic plaques, and smooth muscle cells (SMCs) contribute to plaque stability, selective clearance of macrophages in atherosclerotic plaques is a promising strategy for plaque stabilization. In the present study, we investigated the effects of fluvastatin, simvastatin, lovastatin, and pravastatin on the viability of macrophages and SMCs. All statins, except pravastatin, induced cell death of J774A.1 macrophages after 24 hours, albeit with different sensitivity. The viability of rabbit aortic SMCs was hardly affected. Fluvastatin-induced macrophage cell death was characterized as apoptosis and could be reversed by isoprenoid intermediates of the mevalonate pathway. Peritoneal macrophages from male or female mice were much more resistant to statin-induced cell death. The high sensitivity of J774A.1 macrophages to statin-induced cell death was related to the strong 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in these cells. Macrophage and SMC content of rabbit atherosclerotic plaques was not affected after in vitro treatment with fluvastatin or lovastatin for 3 days. In conclusion, fluvastatin, simvastatin, and lovastatin, but not pravastatin, can selectively induce apoptosis in J774A.1 macrophages, but not in SMCs, primary macrophages or rabbit atherosclerotic plaques. This effect was related to the degree of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in the different cell types. © 2010 Lippincott Williams & Wilkins, Inc.