Effect of the hypothyroid condition on the activation of the TLR4/MYD88/NF-KB signaling pathway in the heart of mice

• Grant number: 23/10345-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2023
• End date: September 30, 2024
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria Luiza de Morais Barreto de Chaves
• Grantee: Beatriz dos Santos Almeida
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 19/17031-2 - Inflammasome in the cardiac physiopathology, AP.TEM

Abstract

Thyroid hormones (TH) are of great importance for the regulation of several mechanisms of the human organism, the heart being the main target of action of these hormones. In this sense, thyroid dysfunction has a profound impact on thecardiovascular system. Hypothyroidism, a condition where HT production is reduced, causes several cardiac morpho-functional alterations, which may be associated with changes in the pattern of inflammatory markers in the heart. Our research group comes working to analyze the relationship of pathways linked to inflammation and cardiovascular changes resulting from thyroid disorders. We previously demonstrated that the TLR4-Myd88-NFkB, related to innate immune response mechanisms, is involved in cardiac hypertrophy induced by high levels of TH. Whereas the status ofhypothyroidism may contribute to the increase of inflammatory markers in the tissue heart, it is possible that this pathway also has an important influence on changes observed in these conditions. In this sense, the objective of this work is to evaluate whether the situation of hypothyroidism, which is accompanied by changes in the parameterscardiac morpho-functional functions, leads to activation of TLR4-Myd88-NFkB pathway signaling, in mice. For this, wild mice will be treated with methimazole to induce hypothyroidism and the morphology and cardiac function of these animals will be evaluated, as well as the protein expression of TLR4, Myd88 and NFkB.