This Article Full Text Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map 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 HighWire Citing Articles via Google Scholar Google Scholar Articles by Corsini, A. Articles by Fumagalli, R. Search for Related Content PubMed PubMed Citation Articles by Corsini, A. Articles by Fumagalli, R.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:420-428.)
© 1995 American Heart Association, Inc.

Articles

Effects of 26-Aminocholesterol, 27-Hydroxycholesterol, and 25-Hydroxycholesterol on Proliferation and Cholesterol Homeostasis in Arterial Myocytes

A. Corsini; D. Verri; M. Raiteri; P. Quarato; R. Paoletti; R. Fumagalli

From the Institute of Pharmacological Sciences, University of Milan, Milan, Italy.

Correspondence to Dr Alberto Corsini, Institute of Pharmacological Sciences, University of Milan, Via Balzaretti 9, 20133 Milan, Italy.

Abstract The major relation existing between cell growth and cholesterol homeostasis prompted us to investigate the effect of 26-aminocholesterol (26-NH₂), 27-hydroxycholesterol (27-OH), and 25-hydroxycholesterol (25-OH) on these cellular events. To test this relation, we incubated human and rat arterial myocytes with the sterols for 72 hours. All the tested compounds (0.5 to 7.5 µmol/L) inhibited rat and human myocyte proliferation and cholesterol biosynthesis in a dose-dependent manner. 26-NH₂ was more potent than oxysterols in inhibiting human myocyte proliferation but equieffective in rat cells; 27-OH and 25-OH displayed similar activity in both cell lines. Inhibition of nuclear incorporation of thymidine in rat myocytes is consistent with decreased cell count. The antiproliferative effect of the tested sterols was reversible. The high inhibition (80%) of cholesterol biosynthesis necessary to induce a decrease in myocyte proliferation suggests a causal relation between the cholesterol synthetic pathway and these cellular processes. In addition, all the tested sterols were able to inhibit hydroxymethyl glutaryl–coenzyme A reductase activity in intact myocytes but not in cell-free extracts. The finding that 26-NH₂ but not 27-OH or 25-OH does not suppress LDL receptor activity in either human or rat myocytes supports the achievement of selectivity over the coordinately regulated LDL receptor gene. The ability of 26-NH₂ to interfere with myocyte proliferation and cholesterol synthesis without affecting the LDL receptor pathway confers at least in vitro a pharmacological interest on the compound in the process of atherogenesis.

Key Words: cholesterol synthesis • LDL receptor • oxysterols • smooth muscle cells • hydroxymethyl glutaryl–coenzyme A reductase

This article has been cited by other articles:

				Y. Ma, L. Xu, D. Rodriguez-Agudo, X. Li, D. M. Heuman, P. B. Hylemon, W. M. Pandak, and S. Ren 25-Hydroxycholesterol-3-sulfate regulates macrophage lipid metabolism via the LXR/SREBP-1 signaling pathway Am J Physiol Endocrinol Metab, December 1, 2008; 295(6): E1369 - E1379. [Abstract] [Full Text] [PDF]

				N. Ferri, A. Granata, C. Pirola, F. Torti, P. J. Pfister, R. Dorent, and A. Corsini Fluvastatin Synergistically Improves the Antiproliferative Effect of Everolimus on Rat Smooth Muscle Cells by Altering p27Kip1/Cyclin E Expression Mol. Pharmacol., July 1, 2008; 74(1): 144 - 153. [Abstract] [Full Text] [PDF]

				X. Li, W. M. Pandak, S. K. Erickson, Y. Ma, L. Yin, P. Hylemon, and S. Ren Biosynthesis of the regulatory oxysterol, 5-cholesten-3{beta},25-diol 3-sulfate, in hepatocytes J. Lipid Res., December 1, 2007; 48(12): 2587 - 2596. [Abstract] [Full Text] [PDF]

				M McMahon, J Grossman, W Chen, and B H Hahn Inflammation and the pathogenesis of atherosclerosis in systemic lupus erythematosus Lupus, November 1, 2006; 15(11_suppl): 59 - 69. [Abstract] [PDF]

				S. Ren, P. Hylemon, Z.-P. Zhang, D. Rodriguez-Agudo, D. Marques, X. Li, H. Zhou, G. Gil, and W. M. Pandak Identification of a novel sulfonated oxysterol, 5-cholesten-3{beta},25-diol 3-sulfonate, in hepatocyte nuclei and mitochondria J. Lipid Res., May 1, 2006; 47(5): 1081 - 1090. [Abstract] [Full Text] [PDF]

				N. B. Javitt 25R,26-Hydroxycholesterol revisited: synthesis, metabolism, and biologic roles J. Lipid Res., May 1, 2002; 43(5): 665 - 670. [Abstract] [Full Text] [PDF]

				A. B. Reiss, N. W. Awadallah, S. Malhotra, M. C. Montesinos, E. S. L. Chan, N. B. Javitt, and B. N. Cronstein Immune complexes and IFN-{gamma} decrease cholesterol 27-hydroxylase in human arterial endothelium and macrophages J. Lipid Res., November 1, 2001; 42(11): 1913 - 1922. [Abstract] [Full Text] [PDF]

				G. J. Schroepfer Jr. Oxysterols: Modulators of Cholesterol Metabolism and Other Processes Physiol Rev, January 1, 2000; 80(1): 361 - 554. [Abstract] [Full Text] [PDF]

				E. R. Wohlfeil and W. B. Campbell 25-Hydroxycholesterol Increases Eicosanoids and Alters Morphology in Cultured Pulmonary Artery Smooth Muscle and Endothelial Cells Arterioscler Thromb Vasc Biol, December 1, 1999; 19(12): 2901 - 2908. [Abstract] [Full Text] [PDF]

				M. Raiteri, L. Arnaboldi, P. Mcgeady, M. H. Gelb, D. Verri, C. Tagliabue, P. Quarato, P. Ferraboschi, E. Santaniello, R. Paoletti, et al. J. Pharmacol. Exp. Ther., June 1, 1997; 281(3): 1144 - 1153. [Abstract] [Full Text]