Published Online
on December 16, 2002

A more recent version of this article appeared on February 4, 2003

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Submitted on August 5, 2002
Revised on September 17, 2002
Accepted on October 7, 2002

Acetylsalicylic Acid Inhibits Cell Proliferation by Involving Transforming Growth Factor-

Santiago Redondo BSc, Carlos G. Santos-Gallego BSc, Patricia Ganado PharmD, Marta García BSc, Laura Rico BSc, Marcela Del Rio PhD, and Teresa Tejerina MD, PhD^*

From the Department of Pharmacology (S.R., C.G.S.-G., P.G., T.T.), School of Medicine, Universidad Complutense, and Epithelial Damage, Repair and Tissue Engineering (M.G., L.R., M.D.R.), CIEMAT, Madrid, Spain.

^* To whom correspondence should be addressed. E-mail: teje{at}med.ucm.es.

Background—Acetylsalicylic acid (ASA) inhibits cell proliferation. This may be mediated by transforming growth factor- (TGF-). TGF- directly stops cell proliferation, restrains cells in G, and inhibits the uptake of platelet-derived growth factor and insulin-like growth factor. These effects are identical to those observed with ASA treatment.

Methods and Results—We cultured rat thoracic aorta vascular smooth muscle cells and measured cytotoxicity, cell proliferation, cell cycle, transcription of TGF-₁, and concentration of TGF-₁ in supernatant medium. ASA dose-dependently restrained cells in G phase with no cytotoxic effect and inhibited cell proliferation by 30.86%. Anti-TGF-₁ reversed this inhibition by 30.21%. However, ASA treatment decreased TGF-₁ transcription and had no significant effect on TGF-₁ concentration.

Conclusions—TGF- seems to play an important role in ASA-mediated inhibition of cell proliferation. Therefore, treatment with ASA prevents coronary disease not only by means of its antiplatelet properties but also by an important inhibition of plaque growth. This relationship between ASA and TGF- explains many other effects, such as cancer chemoprevention, immunomodulation, and wound healing. The aim of this study was to demonstrate this link.

Key words: aspirin • cells • aorta • transforming growth factor beta

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