Details

Autor(en) / Beteiligte

• Koch, Sheryl E
• Nieman, Michelle L
• Robbins, Nathan
• Slone, Samuel
• Worley, Mariah
• Green, Lisa C
• Chen, Yamei
• Barlow, Alexandria
• Tranter, Michael
• Wang, HongSheng
• Lorenz, John N
• Rubinstein, Jack

Titel

Tranilast blunts the hypertrophic and fibrotic response to increased afterload independent of cardiomyocyte transient receptor potential vanilloid 2 channels

Ist Teil von

• Journal of cardiovascular pharmacology, 2018-07, Vol.72 (1), p.40-48

Ort / Verlag

United States: Copyright Wolters Kluwer Health, Inc. All rights reserved

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• ABSTRACTTranilast is clinically indicated for the treatment of allergic disorders and is also a non-selective blocker of the Transient Receptor Potential Vanilloid 2 (TRPV2) channel. Prior studies have found that it has protective effects in various animal models of cardiac disease. Our laboratory has found that genetic deletion of TRPV2 results in a blunted hypertrophic response to increased afterload, thus this study tested the hypothesis that tranilast through cardiomyocyte TRPV2 blockade can inhibit the hypertrophic response to pressure overload in-vivo via transverse aortic constriction and ex vivo via isolated myocyte studies.The in vivo studies demonstrated that tranilast blunted the fibrotic response to increased afterload and to a lesser extent the hypertrophic response. After 4 weeks, this blunting was associated with improved cardiac function, though at 8 weeks the cardiac function deteriorated similarly to the control group. Lastly, the in vitro studies demonstrated that tranilast was not inhibiting these responses at the cardiomyocyte level. In conclusion, we demonstrated that tranilast blunting of the fibrotic and hypertrophic response occurs independently of cardiac TRPV2 channels and may be cardioprotective in the short term but not after prolonged administration.