Alterations in cardiac cells induced by conditioned medium by renal cells treated with P-cresyl sulfate toxin: in vitro cardiorenal syndrome model

• Grant number: 22/12289-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2023
• End date: January 31, 2024
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Marcela Sorelli Carneiro Ramos
• Grantee: Beatriz Favero Bedin
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

Cardiovascular diseases (CVD) are the cause of most deaths, due not only to genetic factors, but above all, environmental factors, due to the modern lifestyle. However, they may be secondary to other diseases, such as cardiorenal syndromes (SCRs). Cardiorenal syndromes are diseases that demonstrate the intense connection between the functioning of the kidneys and the heart and are subdivided into five categories. Cardiorenal Syndrome Type 3 (CRS 3) is characterized by acute kidney injury that triggers damage to heart tissue. One of the injuries that can generate this type of disease is the ischemia and reperfusion injury, very common in hemorrhagic shock and kidney transplants. Although many factors compose the pathophysiology of this syndrome, our laboratory has already identified the great relevance of the immune system and oxidative stress in cardiac alterations induced by ischemic kidney injury. In this sense, the immune system, through the pro-inflammatory cytokines IL-6 and IL-1², promotes cardiac structural changes such as cardiac hypertrophy, in addition to electrical changes. Another type of kidney injury is associated with high levels of uremic compounds, such as Indoxyl Sulfate and P-cresyl sulfate (PCS), common in dialysis patients. These compounds play an important role in the inflammatory status and modulation of cardiac trophism. Considering that: i) the cellular and molecular mechanisms involved in the development of SCR 3 are still not completely known and ii) in vitro models are capable of providing a better understanding of the cellular mechanisms involved in pathologies of the cardio/renal axis; the present study aims to evaluate the role of PCS uremic toxin in cardiomyocyte alterations in vitro. Therefore, we will use culture models of renal cells that will be treated with PCS, subsequently, we will perform the treatment of cardiomyocytes with the culture medium conditioned by renal cells previously submitted to PCS. Molecular parameters related to cardiac trophism will be evaluated, as well as parameters related to inflammatory status.