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From metabolomics to treatment: novel approaches to understand heart failure

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)

Articles published in Agência FAPESP Newsletter about the research grant:
Bacteria can replace chemical fertilizer to protect the natural environment 
Articles published in other media outlets (3 total):
Harvard Medical School (EUA): Revving the Engine (27/Jan/2020)
Scienmag Science Magazine (Reino Unido): Revving Up The Engine (27/Jan/2020)
Health News Digest (EUA): Scientists Trace the Molecular Roots of Potentially Fatal Heart Condition (27/Jan/2020)

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)
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; MCGEACHIE, MICHAEL; MOORE, STEVEN C.; KRAFT, PETER; MATHE, EWY; LASKY-SU, JESSICA; WORK, CONSORTIUM METAB STUDIES STAT. Integration of Metabolomic and Other Omics Data in Population-Based Study Designs: An Epidemiological Perspective. METABOLITES, v. 9, n. 6 JUN 2019. Web of Science Citations: 3.
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. Web of Science Citations: 0.

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