TLR4 and complement system : possible key mechanism in renal ischemia/reperfusion induced cardiac hypertrophy

• Grant number: 15/19107-5
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2016
• End date: June 30, 2018
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Marcela Sorelli Carneiro Ramos
• Grantee: Marcela Sorelli Carneiro Ramos
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

The immune system interacts with several different tissues and organs of the human body, for example, the heart tissue. In diseases that generate a systemic inflammation, some factors are released in the blood stream and they are able to reach the most diverse organs, promoting interaction between tissue cells and immunity cells. It is known that renal insufficiency (RI) is characterized by generation of systemic inflammation, whereas it might reach the heart tissue, leading to a series of alterations. The local response can be initiated by receptors named Toll-like [TLRs - recognizers of pathogen-associated molecular patterns (PAMPs) or danger associated molecular patterns (DAMPs)], via complement system or combined responses. During inflammation, the complement system component C3a is released in large amounts and binds to its receptor C3aR1, which is able to assist in the TLRs activation, inducing transcription of inflammatory factors throughout translocation of the nuclear factor kappa B (NF-ºB) to the nucleus. Such process can be facilitated by a kinase named Ca2+/calmodulin-dependent protein kinase type II delta (CaMKII´ which, in turn, helps in the NF-ºB activation and then translocation to the nucleus. Although the majority of studies related to CaMKII´ are directed to its participation in cardiac calcium homeostasis, new studies have been demonstrating alternative actions, such as transcription of complement system factor B via TLR4 stimulation. Based on above considerations, the present work aims to evaluate the interaction between complement system and TLR4 on cardiac hypertrophy development induced by renal ischemia/reperfusion; Therefore, it was be performed procedure of unilateral renal pedicle occlusion during 60 min, followed by reperfusion of 8, 12 or 15 days. Analysis of gene expression reveals altered levels of SC components (from classic and alternative pathways) as well as CaMKII´ suggesting a role of SC in cardiac hypertrophy induced by renal ischemia-reperfusion. (AU)

Scientific publications

(16)

(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)

G.M. ARMENTANO; M.S. CARNEIRO-RAMOS. Effect of COVID-19 on cardiorenal axis: known or unknown universe?. Brazilian Journal of Medical and Biological Research, v. 55, 2022-03-21. (08/10175-4, 15/19107-5, 19/11077-0)

CRUZ JUNHO, V, C.; TRENTIN-SONODA, M.; ALVIM, J. M.; GAISLER-SILVA, F.; CARNEIRO-RAMOS, M. S.. Ca(2+/)Calmodulin-dependent kinase II delta B is essential for cardiomyocyte hypertrophy and complement gene expression after LPS and HSP60 stimulation in vitro. Brazilian Journal of Medical and Biological Research, v. 52, n. 7, 2019. (16/11865-0, 15/19107-5, 15/01792-3, 14/16908-4)

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)

TRENTIN-SONODA, MAYRA; FRATONI, FRAYLI MALTONI; DA CRUZ JUNHO, CAROLINA VICTORIA; SILVA, WELLINGTON CAIO; PANICO, KARINE; CARNEIRO-RAMOS, MARCELA SORELLI. Caspase-1 as Molecular Key in Cardiac Remodeling during Cardiorenal Syndrome Type 3 in the Murine Model. CURRENT MOLECULAR MEDICINE, v. 20, n. 1, p. 72-78, 2020. (15/15832-7, 15/19107-5)

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)

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)

NERES-SANTOS, RAQUEL SILVA; JUNHO, CAROLINA VICTORIA CRUZ; PANICO, KARINE; CAIO-SILVA, WELLINGTON; PIERETTI, JOANA CLAUDIO; TAMASHIRO, JULIANA ALMEIDA; SEABRA, AMEDEA BAROZZI; RIBEIRO, CESAR AUGUSTO JOAO; CARNEIRO-RAMOS, MARCELA SORELLI. Mitochondrial Dysfunction in Cardiorenal Syndrome 3: Renocardiac Effect of Vitamin C. CELLS, v. 10, n. 11, NOV 2021. (15/25541-0, 18/08194-2, 19/11077-0, 20/03646-2, 15/19107-5)

GAISLER-SILVA, FERNANDA; CRUZ JUNHO, CAROLINA VICTORIA; FREDO-DA-COSTA, IZABELLE; CHRISTOFFOLETE, MARCELO AUGUSTO; CARNEIRO-RAMOS, MARCELA SORELLI. Diet-induced Obesity Differentially Modulates Cardiac Inflammatory Status in the C57 and FVB Mouse Strains. CURRENT MOLECULAR MEDICINE, v. 22, n. 4, p. 9-pg., 2022-01-01. (15/02052-3, 15/19107-5, 18/07811-8, 19/11077-0)

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)

CAIO-SILVA, WELLINGTON; JUNHO, CAROLINA V. DA CRUZ; PANICO, KARINE CRUZ; CARNEIRO-RAMOS, MARCELA SORELLI. Nitric Oxide and Nitric Oxide Synthase isoforms are modulated in renal ischemia/reperfusion induced cardiac hypertrophy. FASEB JOURNAL, v. 33, p. 2-pg., 2019-04-01. (15/19107-5)

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)

C.V. CRUZ JUNHO; M. TRENTIN-SONODA; J.M. ALVIM; F. GAISLER-SILVA; M.S. CARNEIRO-RAMOS. Ca2+/Calmodulin-dependent kinase II delta B is essential for cardiomyocyte hypertrophy and complement gene expression after LPS and HSP60 stimulation in vitro. Brazilian Journal of Medical and Biological Research, v. 52, n. 7, 2019-07-15. (16/11865-0, 15/19107-5, 15/01792-3, 14/16908-4)

CIRINO-SILVA, ROGERIO; KMIT, FERNANDA V.; TRENTIN-SONODA, MAYRA; NAKAMA, KARINA K.; PANICO, KARINE; ALVIM, JULIANA M.; DREYER, THIAGO R.; MARTINHO-SILVA, HERCULANO; CARNEIRO-RAMOS, MARCELA S.. Renal ischemia/reperfusion-induced cardiac hypertrophy in mice: Cardiac morphological and morphometric characterization. JRSM CARDIOVASCULAR DISEASE, v. 6, JAN 1 2017. (15/19107-5)

ARMENTANO, G. M.; CARNEIRO-RAMOS, M. S.. Effect of COVID-19 on cardiorenal axis: known or unknown universe?. Brazilian Journal of Medical and Biological Research, v. 55, n. 1, p. 6-pg., 2022-01-01. (15/19107-5, 19/11077-0, 08/10175-4)

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)

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)