Cardiorenal syndrome and inflammation: missing links in hypothyroidism?

• Grant number: 24/21516-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2025
• End date: April 30, 2028
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Marcela Sorelli Carneiro Ramos
• Grantee: Aline Cristina Parletta
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

Hypothyroidism is a highly prevalent disease that affects different systems in the body. In the heart, hypothyroidism causes bradycardia, diastolic dysfunction, atrophy, and cardiac fibrosis. In the kidneys, hypothyroidism impairs the blood filtration capacity, causing renal atrophy and fibrosis. Cardiac and renal dysfunctions are closely related and this relationship is currently defined as cardiorenal syndrome (CRS). This condition is not fully understood, but it is known that CRS is mediated by the activation of the immune system. Although there is strong evidence that hypothyroidism is accompanied by the development of CRS, there are no studies exploring this relationship in an integrated manner. In this sense, the objective of the present study is to characterize hypothyroidism-induced CRS and evaluate the role of inflammation in this context. To this, mice will be treated with 0.1% methimazole and 1% sodium perchlorate in drinking water to induce hypothyroidism for 4, 8 or 12 weeks. Cardiac function will be assessed by echocardiography. Renal function will be measuring by serum urea and creatinine levels and analyzing markers of renal injury. Cardiac and renal morphology will be assessed by histology. Inflammation will be assessed by flow cytometry and cytokine levels. Potential biomarkers associated with cardiac and renal changes caused by hypothyroidism will be investigated by Fourier transform infrared spectroscopy (FTIR). Given the high clinical incidence and the lack of studies in this context, the present proposal may contribute with new data on changes associated with hypothyroidism.