Role of the Klotho/FGF23 axis in the development of Type 3 Cardiorenal Syndrome induced by ischemic renal injury

• Grant number: 18/03089-6
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: July 01, 2018
• End date: July 31, 2022
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Marcela Sorelli Carneiro Ramos
• Grantee: Carolina Victória da Cruz Junho
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
• Associated scholarship(s): 18/19204-9 - Effects of the silencing and super-expressing of Klotho gene in cardiac function through hypertrophy induced by cardiorenal syndrome, BE.EP.DD

Abstract

In diseases that generate an inflammatory situation, such as Cardiorenal Syndrome, different clinical conditions promote cardiac and renal dysfunction. It has five different types and the first two (types 1 and 2) are associated anormalities in cardiac function that cause injury or renal dysfunction; type 3 and 4 are characterized by renal insults that subject the heart to dysfunctions; the ype 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 picture 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 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, a detailed and systematic study of the Klotho/FGF axis23 and its subsequent action in the face of the cardiovascular alterations induced by renal injury is necessary. 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

(7)

(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)

FALCONI, CARLOS ALEXANDRE; JUNHO, CAROLINA VICTORIA DA CRUZ; FOGACA-RUIZ, FERNANDA; VERNIER, IMARA CARIDAD STABLE; DA CUNHA, REGIANE STAFIM; STINGHEN, ANDREA EMILIA MARQUES; CARNEIRO-RAMOS, MARCELA SORELLI. Uremic Toxins: An Alarming Danger Concerning the Cardiovascular System. FRONTIERS IN PHYSIOLOGY, v. 12, MAY 14 2021. (19/11077-0, 15/19107-5, 18/03089-6)

CRUZ JUNHO, CAROLINA VICTORIA; TRENTIN-SONODA, MAYRA; PANICO, KARINE; NERES DOS SANTOS, RAQUEL SILVA; ABRAHAO, MARIANA VIEIRA; STABLE VERNIER, IMARA CARIDAD; FURSTENAU, CRISTINA RIBAS; CARNEIRO-RAMOS, MARCELA SORELLI. Cardiorenal syndrome: long road between kidney and heart. HEART FAILURE REVIEWS, v. N/A, p. 17-pg., 2022-02-08. (19/11077-0, 18/03089-6, 15/19107-5, 08/10175-4)

CRUZ JUNHO, CAROLINA VICTORIA; BUENO AZEVEDO, CAROLINA AMARAL; DA CUNHA, REGIANE STAFIM; DE YURRE, AINHOA RODRIGUEZ; MEDEI, EMILIANO; MARQUES STINGHEN, ANDREA EMILIA; CARNEIRO-RAMOS, MARCELA SORELLI. Heat Shock Proteins: Connectors between Heart and Kidney. CELLS, v. 10, n. 8, AUG 2021. (08/10175-4, 18/03089-6, 19/11077-0, 15/19107-5)

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)

PIERETTI, JOANA CLAUDIO; CRUZ JUNHO, CAROLINA VICTORIA; CARNEIRO-RAMOS, MARCELA SORELLI; SEABRA, AMEDEA BAROZZI. H2S- and NO-releasing gasotransmitter platform: A crosstalk signaling pathway in the treatment of acute kidney injury. PHARMACOLOGICAL RESEARCH, v. 161, NOV 2020. (18/02832-7, 18/03089-6, 18/08194-2, 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)

JUNHO, CAROLINA V. DA CRUZ; CAIO-SILVA, WELLINGTON; RUIZ-HURTADO, GEMA; CARNEIRO-RAMOS, MARCELA SORELLI. Characterization of Klotho/FGF23 signaling in cardiorenal syndrome-induced cardiac hypertrophy. FASEB JOURNAL, v. 33, p. 2-pg., 2019-04-01. (18/03089-6, 15/19107-5)