Role of cardiac MyD88 on cardiac hypertrophy induced by tyroid hormone: model of specific tissue deletion induced by tamoxifen (Cre-Lox system)

• Grant number: 16/24403-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2017
• End date: December 31, 2018
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria Luiza de Morais Barreto de Chaves
• Grantee: Aline Cristina Parletta
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Cardiac hypertrophy, despite being an adaptive response may contribute to cardiomyopathy development and progression. It is well established that thyroid hormones exert direct and indirect effects on the heart, which result on an hypertrophic state of this organ. In this sense, our research group has been studying the various cellular and molecular mechanisms involved in this process. Recently, our group showed that cardiac hypertrophy induced by thyroid hormones is accompanied by the activation of factors related to inflammation, among which MyD88 stands out. This relation between cardiac hypertrophy and inflammation-related pathways has already been evidenced in other experimental models, especially those involving pressure overload. In this study, genetically modified mice with induced cardiac MyD88 deletion will be treated with thyroid hormone (T3, 7¼g/100g body weight/day) for 14 days. BP and HR will be monitored by tail plethysmography throughout the treatment. After euthanasia, the hearts will be removed and the tissues will be processed for histological analysis. Thus, through the Cre / LoxP system, which allows the inducible deletion of MyD88 exclusively in the heart, the present work aims to uncover the role of this molecule in thyroid hormone-induced cardiac hypertrophy, providing information to contribute to the advancement of knowledge regarding cellular and molecular mechanisms affecting the cardiomyocyte. (AU)