TGF-beta1-induced thrombospondin-1 expression through the p38 MAPK pathway is abolished by fluvastatin in human coronary artery smooth muscle cells

Vascular Pharmacology
Fiona C McGillicuddyAlan K Keenan

Abstract

Thrombospondin-1 (TSP-1) and transforming growth factor-beta1 (TGF-beta1) are both implicated in the pathogenesis of in-stent restenosis. This study evaluated the hypothesis that the HMG-CoA reductase inhibitor fluvastatin inhibits TGF-beta1 induced TSP-1 expression via inhibition of p38 mitogen activated protein kinase (MAPK) phosphorylation in human coronary artery smooth muscle cells (HCASMC) and may therefore have anti-restenosis potential. Fluvastatin significantly reduced TSP-1 mRNA and protein expression in HCASMC in a concentration-dependent manner with a significant reduction in expression observed after treatment with 0.25 microM fluvastatin. TGF-beta1 (5 ng/ml) induced phosphorylation of p38 MAPK and induced TSP-1 mRNA and protein expression in HCASMC. Fluvastatin abolished TGF-beta1-induced phosphorylation of p38 MAPK and TGF-beta1-induced TSP-1 expression. Blockade of the p38 MAPK pathway with the upstream inhibitor SB-203580 also abolished TGF-beta1-induced TSP-1 expression. We conclude that fluvastatin decreases expression of TSP-1 and abolishes the ability of TGF-beta1 to induce TSP-1 expression in HCASMC; this may be achieved by preventing signalling through the p38 MAPK pathway. Targeted delivery of fluvastati...Continue Reading

References

Oct 1, 1991·Current Opinion in Cell Biology·W A Frazier
Nov 24, 1995·Science·Z XiaM E Greenberg
Feb 23, 1995·The New England Journal of Medicine·T J AndersonP Ganz
Jun 6, 1997·The Journal of Biological Chemistry·J B CrawleyB M Foxwell
Nov 14, 1997·Arteriosclerosis, Thrombosis, and Vascular Biology·M K PatelA D Hughes
Apr 16, 1998·The Journal of Surgical Research·J J RothG P Tuszynski
Jun 4, 1999·Progress in Biophysics and Molecular Biology·M H Cobb
Aug 14, 1999·The Journal of Biological Chemistry·J C HedgesW T Gerthoffer
Apr 19, 2000·Hypertension Research : Official Journal of the Japanese Society of Hypertension·H ChenK Shimada
Jan 12, 2001·Physiological Reviews·Y TakaiT Matozaki
Feb 22, 2001·International Journal of Cardiology·J MusialA Szczeklik
Jun 30, 2001·The New England Journal of Medicine·P M RidkerUNKNOWN Air Force/Texas Coronary Atherosclerosis Prevention Study Investigators
Aug 11, 2001·Arteriosclerosis, Thrombosis, and Vascular Biology·L DiomedeM Salmona
Jun 26, 2002·Circulation·Alan C Yeung, Philip Tsao
Jan 28, 2003·Lancet·Rossella Fattori, Tommaso Piva
Aug 11, 2004·Circulation·Andrew FarbRenu Virmani
Mar 1, 2005·Biochimie·F BostB Binétruy
Apr 19, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Natalya V NarizhnevaTatiana V Byzova

❮ Previous
Next ❯

Citations

Sep 24, 2010·Journal of Oncology·Hironobu YamashitaVito Quaranta
Oct 4, 2008·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Marjan BoermaMartin Hauer-Jensen
Mar 8, 2012·Korean Circulation Journal·Kyu-Young ChoiJae-Hyung Kim
Aug 9, 2007·Nephron. Experimental Nephrology·Michael R BennettS Steven Potter
Jan 29, 2008·The Journal of Biological Chemistry·Harsha DadlaniPeter J Little
May 18, 2012·American Journal of Physiology. Cell Physiology·Ronaldo J ChavezPriya Raman
Apr 30, 2020·Journal of Cellular Biochemistry·Furqan MuqriVivian Gahtan
Nov 30, 2007·American Journal of Physiology. Renal Physiology·Klaudia GiehlMargarete Goppelt-Struebe
Oct 24, 2012·Journal of Cardiovascular Pharmacology and Therapeutics·Mojca LunderMišo Šabovič
Jul 7, 2020·Journal of Diabetes Research·Linhao XuYizhou Xu

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here