Role of the NLRP3 inflammasome in models associated with cardiac remodeling.

Author(s)

Aline Cristina Parletta Cesaro

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2024-07-02

Examining board members

Maria Luiza de Morais Barreto de Chaves; Eliana Hiromi Akamine; Vagner Roberto Antunes; Caroline Serrano do Nascimento

• Advisor: Maria Luiza de Morais Barreto de Chaves

Abstract

Cardiac remodeling (CR) corresponds to a set of cardiac changes related to the size, shape and/or function of the heart, which occurs after a stressful stimulus. CR is an important risk factor for the development of cardiovascular diseases and therefore represents an interesting moment for therapeutic intervention. Increasing evidence in the literature has demonstrated the participation of innate immune response mechanisms, especially the NLRP3 inflammasome, in cardiac pathologies. However, its role in CR is not well established. In this sense, the present study aims to evaluate, in mice, the role of the NLRP3 inflammasome in three different CR models: induced by hyperthyroidism, hypothyroidism, or beta-adrenergic stimulation. For this, wild-type (WT) and NLRP3 knockout (NLRP3-KO) were treated with triiodothyronine (T3, 7g/100g), methimazole (0,05%) or isoproterenol (ISO, 60mg/kg). Cardiac morphology was assessed by histology and cardiac function by echocardiography, protein expression was assessed by western blotting and gene expression was analyzed by real-time PCR. Regarding the hyperthyroidism, we demonstrated that T3-induced cardiac hypertrophy (CH) is accompanied by reduction of NLRP3 in the heart of WT mice, and that deficiency of NLRP3 (NLRP3-KO) does not influences T3-induced CH. Regarding hypothyroidism, interestingly, WT mice did not show changes in cardiac morphology or function, indicating a difficulty in installing the model. Regarding ISO-induced CR, NLRP3-KO mice were protected from ISO-induced fibrosis and mortality. Furthermore, in the hearts of NLRP3-KO mice the ISO-induced increase in IL-1 gene expression was prevented. Based on our data, it can be concluded that: 1) T3-induced CH occurs independently of the NLRP3 inflammasome; 2) Hypothyroidism did not induce cardiac remodeling in our study; 3) NLRP3 deficiency prevents ISO-induced fibrosis and mortality. (AU)

• FAPESP's process: 21/06151-7 - Role of NLRP3 inflammasome on the cardiac function in Hypothyroid animals
• Grantee: Aline Cristina Parletta
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)