Acetylsalicylic Acid Inhibits Cell Proliferation by Involving Transforming Growth Factor-

Background—Acetylsalicylic acid (ASA) inhibits cell proliferation. This may be mediated by transforming growth factor(TGF). TGFdirectly stops cell proliferation, restrains cells in G0, 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 TGF1, and concentration of TGF1 in supernatant medium. ASA dose-dependently restrained cells in G0 phase with no cytotoxic effect and inhibited cell proliferation by 30.86%. Anti–TGF1 reversed this inhibition by 30.21%. However, ASA treatment decreased TGF1 transcription and had no significant effect on TGF1 concentration. Conclusions—TGFseems 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 TGFexplains many other effects, such as cancer chemoprevention, immunomodulation, and wound healing. The aim of this study was to demonstrate this link. (Circulation. 2003;107:626-629.)