From metabolomics to treatment: novel approaches to understand heart failure

• Grant number: 17/20593-7
• Support Opportunities: Research Grants - Research Partnership for Technological Innovation - PITE
• Start date: September 01, 2018
• End date: August 31, 2022
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Agreement: Agilent
• Principal Investigator: Alexandre da Costa Pereira
• Grantee: Alexandre da Costa Pereira
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Company: Agilent Technologies Brasil Ltda
• City: São Paulo
• Associated researchers: Cristine E. Seidman ; José Eduardo Krieger ; Karina Helena Morais Cardozo ; Valdemir Melechco Carvalho

Abstract

Heart failure (HF) is a national and global epidemic affecting millions of patients worldwide. HF is characterized by intense remodeling of the myocardium and important metabolic changes in cardiomyocyte biology. These changes are thought to be both a cause and consequence of the remodeling process and, thus, important targets for new pharmacological therapies. It is thus critically important that a detailed understanding of not only the main metabolic pathways altered in these disease states, but also the correlation structure of these changes with other impending systemic changes and embodied by transcriptional, epigenetic and functional remodeling of cardiomyocytes during the heart remodeling process is incorporated into our models of disease pathology. We propose to integrate metabolomics, functional, and molecular analyses of cell and animal model harboring genetic variants known to cause cardiomyopathies in humans and combine them with a unique set of animal and iPS-CM models to solve the pressing problem of characterizing metabolic pathways altered in these conditions and integrate these to derive mechanistic insights. This will lead to increased changes of translating this information into new, innovative, and specific therapeutic approaches to heart failure by different etiologies. (AU)

Scientific publications

(4)

(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)

BAPTISTA, ALINE L.; PADILHA, KALLYANDRA; MALAGRINO, PAMELLA A.; VENTURINI, GABRIELA; ZERI, ANA C. M.; DOS REIS, LUCIENE M.; MARTINS, JANAINA S.; JORGETTI, VANDA; PEREIRA, ALEXANDRE C.; TITAN, SILVIA M.; et al. Potential Biomarkers of the Turnover, Mineralization, and Volume Classification: Results Using NMR Metabolomics in Hemodialysis Patients. JBMR PLUS, v. 4, n. 7, p. 9-pg., 2020-07-01. (17/20593-7)

CHU, SU H.; HUANG, MENGNA; KELLY, RACHEL S.; BENEDETTI, ELISA; SIDDIQUI, JALAL K.; ZELEZNIK, OANA A.; PEREIRA, ALEXANDRE; HERRINGTON, DAVID; WHEELOCK, CRAIG E.; KRUMSIEK, JAN; et al. Integration of Metabolomic and Other Omics Data in Population-Based Study Designs: An Epidemiological Perspective. METABOLITES, v. 9, n. 6, JUN 2019. (17/20593-7)

OLIVEIRA, THEO G. M.; VENTURINI, GABRIELA; ALVIM, JULIANA M.; FEIJO, LARISSA L.; DINARDO, CARLA L.; SABINO, ESTER C.; SEIDMAN, JONATHAN G.; SEIDMAN, CHRISTINE E.; KRIEGER, JOSE E.; PEREIRA, ALEXANDRE C.. Different Transcriptomic Response to T. cruzi Infection in hiPSC-Derived Cardiomyocytes From Chagas Disease Patients With and Without Chronic Cardiomyopathy. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 12, p. 12-pg., 2022-07-07. (19/11821-1, 17/13706-0, 17/20593-7)

TITAN, SILVIA M.; VENTURINI, GABRIELA; PADILHA, KALLYANDRA; GOULART, ALESSANDRA C.; LOTUFO, PAULO A.; BENSENOR, ISABELA J.; KRIEGER, JOSE E.; THADHANI, RAVI I.; RHEE, EUGENE P.; PEREIRA, ALEXANDRE C.. Metabolomics biomarkers and the risk of overall mortality and ESRD in CKD: Results from the Progredir Cohort. PLoS One, v. 14, n. 3, MAR 18 2019. (11/17341-0, 15/23445-3, 17/20593-7)