Evaluation of new Thiazolidinediones effects on stem cell derived cardiomyocytes

• Grant number: 11/23292-1
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: April 16, 2012
• End date: December 15, 2012
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Dulcineia Saes Parra Abdalla
• Grantee: Martina Rudnicki
• Supervisor: Jürgen Hescheler
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Cologne (UoC), Germany

Abstract

Thiazolidinediones (TZDs) are a class of drugs used for treatment of type 2 diabetes, but also can exert pleiotropic effects, including anti-inflammatory and vascular protective effects. However, important side-effects such as significant weight gain, increased adiposity, peripheral edema, increased rate of bone fracture and augmented risk of congestive heart failure are associated to TZDs therapy, suggesting that the investigation of alternative TZDs with better pharmacological properties is warranted. By exploring, for the first time, the biological activity of new TZDs, we provide evidence suggesting that the chemical modifications might alter the effects of these new compounds on the angiogenic process. In addition, our data also indicate that, compared to rosiglitazone, the new TZDs display similar anti-inflammatory properties in TNF±-stimulated HUVECs. However, the cardiac effects as well as the cardiotoxicity of the new TZDs remain unknown. By an 8-month cooperation work with Dr. Hescheler, an internationally recognized expert on stem cell research field (University of Cologne, Cologne, Germany), this project aims further exploitation of the cardiac and cardiotoxic effects of new TZDs using techniques not promptly available in Brazil. With this crucial cooperation, questions such as: 1) Do new TZDs show cardiotoxic effects? and 2) Could new TZDs alter the electrophysiological profile of cardiomyocytes or induce cardiomyocyte hypertrophy? can be answered, offering a unique opportunity to complement our findings of a 2-years work in Brazil and the obtainment of new insights into the biological activities of new TZDs as well as its potential clinical use. (AU)