Published ahead of print on January 27, 2005, doi:10.1165/rcmb.2004-0127OC
© 2005 American Thoracic Society DOI: 10.1165/rcmb.2004-0127OC Simvastatin Inhibits Growth Factor Expression and Modulates Profibrogenic Markers in Lung FibroblastsLung Research, Institute of Science and Technology in Medicine, University Hospital of North Staffordshire/Keele University, Stoke on Trent, Staffordshire, United Kingdom; and Department of Obstetrics and Gynecology, Institute of Wound Repair, Health Science Center, University of Florida, Gainesville, Florida Correspondence and requests for reprints should be addressed to Keira Watts, Ph.D., Lung Research, Institute of Science and Technology in Medicine, School of Postgraduate Medicine, Thornburrow Drive, Hartshill, Stoke on Trent ST4 7NQ, UK. E-mail: keira_watts{at}yahoo.co.uk
Simvastatin is best known for its antilipidemic action and use in cardiovascular disease due to its inhibition of 3-hydroxy-3-methylglutaryl CoenzymeA (HMG CoA) reductase, a key enzyme in the cholesterol synthesis pathway. Inhibition of biological precursors in this pathway also enables pleiotrophic immunomodulatory and anti-inflammatory capabilities, including modulation of growth factor expression. Connective tissue growth factor (CTGF) and persistent myofibroblast formation are major determinants of the aggressive fibrotic disease, idiopathic pulmonary fibrosis (IPF). In this study we used human lung fibroblasts derived from healthy and IPF lungs to examine Simvastatin effects on CTGF gene and protein expression, analyzed by RT-PCR and ELISA, respectively. Simvastatin significantly inhibited (P < 0.05) CTGF gene and protein expression, overriding the induction by transforming growth factor-ß1, a known potent inducer of CTGF. Such Simvastatin suppressor action on growth factor interaction was reflected functionally on recognized phenotypes of fibrosis.
Key Words: This article has been cited by other articles:
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
-smooth muscle actin expression was downregulated and collagen gel contraction reduced by 4.94- and 7.58-fold in IMR90 and HIPF lung fibroblasts, respectively, when preconditioned with 10 µM Simvastatin compared with transforming growth factor-ß1 treatment alone after 24 h. Our data suggest that Simvastatin can modify critical determinants of the profibrogenic machinery responsible for the aggressive clinical profile of IPF, and potentially prevents adverse lung parenchymal remodeling associated with persistent myofibroblast formation. 
