Effects of the silencing and super-expressing of Klotho gene in cardiac function through hypertrophy induced by cardiorenal syndrome

• Grant number: 18/19204-9
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: March 11, 2019
• End date: March 10, 2020
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Marcela Sorelli Carneiro Ramos
• Grantee: Carolina Victória da Cruz Junho
• Supervisor: Gema Ruiz Hurtado
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
• Institution abroad: Hospital Universitario 12 De Octubre, Spain
• Associated to the scholarship: 18/03089-6 - Role of the Klotho/FGF23 axis in the development of Type 3 Cardiorenal Syndrome induced by ischemic renal injury, BP.DD

Abstract

The Cardiorenal Syndrome is characterized by the presence of a systemic inflammatory condition where different clinical conditions promote cardiac and renal dysfunction. It has five different types where the first two types (type 1 and 2) are associated with abnormalities in cardiac function that cause injury or renal dysfunction; those of type 3 and 4 that are characterized by renal insults that subject the heart to dysfunctions; the latter type 5 is characterized by systemic diseases that induce both cardiac and renal dysfunctions. It is known that renal insufficiency (IR) and chronic kidney disease (CKD) are characterized by a systemic inflammatory condition that can reach the heart tissue leading to a series of alterations. Among these changes, we can mention the modulation in Klotho levels, a gene that is negatively regulated by fibroblast growth factor 23 (FGF23). Studies indicate that the Klotho/FGF23 axis is closely associated with the cardiorenal syndrome since the systemic inflammation causes the acetylation of histones in the Klotho gene, reducing its expression. This reduction increases FGF23, which in large numbers is detrimental to cardiac function, since it increases the risk of atherosclerosis due to the alteration of phosphate and intracellular calcium homeostasis. Since the cardiorenal syndrome is a clinical picture of a high incidence and relevance in the world population, it is necessary to study in detail the systematic Klotho/FGF axis23 and its subsequent action in the face of cardiovascular alterations induced by renal injury. Considering the above, the objective of this study is to evaluate the participation of this axis in cardiac hypertrophy induced by renal ischemia, mainly evaluating intracellular calcium and EC (excitation-contraction) and ET (excitation transcription) coupling in the heart. To do so, the renal ischemia and reperfusion model in knockout mice for Klotho and superexpressed Klotho will be used, by occlusion of the left renal pedicle for 60 minutes, followed by reperfusion in the short term (for 5, 8 and 15 days) and long term (from 6 to 12 weeks). (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

JUNHO, CAROLINA VICTORIA CRUZ; GONZALEZ-LAFUENTE, LAURA; NAVARRO-GARCIA, JOSE ALBERTO; RODRIGUEZ-SANCHEZ, ELENA; CARNEIRO-RAMOS, MARCELA SORELLI; RUIZ-HURTADO, GEMA. nilateral Acute Renal Ischemia-Reperfusion Injury Induces Cardiac Dysfunction through Intracellular Calcium Mishandlin. NTERNATIONAL JOURNAL OF MOLECULAR SCIENCE, v. 23, n. 4, FEB 2022. (18/19204-9, 18/03089-6, 19/11077-0, 15/19107-5)

CRUZ JUNHO, CAROLINA VICTORIA; GONZALEZ-LAFUENTE, LAURA; SILVA NERES-SANTOS, RAQUEL; ALBERTO NAVARRO-GARCIA, JOSE; RODRIGUEZ-SANCHEZ, ELENA; RUIZ-HURTADO, GEMA; SORELLI CARNEIRO-RAMOS, MARCELA. Klotho relieves inflammation and exerts a cardioprotective effect during renal ischemia/reperfusion-induced cardiorenal syndrome. BIOMEDICINE & PHARMACOTHERAPY, v. 153, p. 13-pg., 2022-08-09. (18/19204-9, 15/19107-5, 18/03089-6, 19/11077-0)