Mevalonate deprivation impairs IGF-I/insulin signaling in human vascular smooth muscle cells

Atherosclerosis
J Martínez-GonzálezL Badimon

Abstract

3-Hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase inhibitors (statins) are therapeutically used to lower plasma cholesterol levels. In addition, these drugs can block vascular smooth muscle cell (VSMC) proliferation. The present study addressed the question whether the inhibitory effect of lovastatin on premitotic DNA synthesis correlates with a downregulation of c-fos mRNA levels, a marker of signaling efficiency, in human SMC. Here we show that in human SMC exposed to individual growth factors (platelet-derived growth factor, epidermal growth factor, alpha-thrombin, insulin, insulin-like growth factor I (IGF-I)) and human serum, the maximal [3H]thymidine incorporation and c-fos mRNA expression are closely correlated. Only alpha-thrombin elicited overexpression of c-fos as compared with its effect on [3H]thymidine incorporation. Lovastatin efficiently inhibited [3H]thymidine uptake promoted by all mitogens tested (76-87%); however, it significantly inhibited upregulation of c-fos mRNA levels induced only by insulin (33-67%, P < 0.05) and IGF-I (31 57%, P < 0.05). This inhibition was overcome by mevalonate and geranylgeraniol, and partially by farnesol. c-fos mRNA expression induced by 4-beta-phorbol-12-myristate-13-ace...Continue Reading

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Citations

Dec 8, 2010·Canadian Journal of Anaesthesia = Journal Canadien D'anesthésie·Sunil X AnandPaul M Heerdt
Jun 14, 2005·Atherosclerosis·Jordi RiusLina Badimon
Feb 9, 2000·Pharmacology & Therapeutics·A CorsiniF Bernini
Nov 18, 2003·Diabetes, Obesity & Metabolism·J SheltonC R White
Oct 18, 2011·Respiratory Research·Omar F AliJohn Wharton
Mar 19, 2014·Clínica e investigación en arteriosclerosis : publicación oficial de la Sociedad Española de Arteriosclerosis·Ricardo Rodriguez-CalvoJosé Martínez-González
Apr 22, 2005·Journal of Thrombosis and Haemostasis : JTH·V Wibaut-BerlaimontR P Naoumova
Jan 1, 2005·Toxicology Mechanisms and Methods·Jerzy Beltowski
Mar 14, 2007·Angiology·Hirotoshi KamishiradoKoichi Node
Jan 7, 2009·Therapeutic Advances in Cardiovascular Disease·Manuel Rodríguez-YáñezJosé Castillo
Oct 16, 1999·Arteriosclerosis, Thrombosis, and Vascular Biology·M ViñalsL Badimon
Feb 10, 2000·Circulation Research·A Bayes-GenisR S Schwartz
Jun 5, 2007·American Journal of Physiology. Lung Cellular and Molecular Physiology·Min LiDeniz Toksoz
Jul 18, 2000·American Journal of Physiology. Cell Physiology·L SandirasegaraneM Kester
Mar 10, 1999·The American Journal of Physiology·D W JohnsonC A Pollock

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