TY - JOUR
T1 - Diet Alters Serum Metabolomic Profiling in the Mouse Model of Chronic Chagas Cardiomyopathy
AU - Lizardo, Kezia
AU - Ayyappan, Janeesh Plakkal
AU - Ganapathi, Usha
AU - Dutra, Walderez O.
AU - Qiu, Yunping
AU - Weiss, Louis M.
AU - Nagajyothi, Jyothi F.
N1 - Funding Information:
We thank Erika Shor at the Public Health Research Institute for the critical reading of the manuscript. We thank Dr. Jeffery Pessin of the Albert Einstein College of Medicine for their moral support in our studies. This study was supported by grants from the National Heart, Lung, and Blood Institute (National Institutes of Health HL-122866) to Jyothi Nagajyothi. We also acknowledge the Stable Isotope and Metabolomics Core Facility of the Diabetes Research and Training Center (DRTC) of the Albert Einstein College of Medicine (supported by the NIH/NCI grant P60DK020541).
Funding Information:
Lizardo Kezia kl698@njms.rutgers.edu 1 Ayyappan Janeesh Plakkal jp1482@njms.rutgers.edu 1 Ganapathi Usha ganapaus@njms.rutgers.edu 1 Dutra Walderez O. waldutra@gmail.com 2 https://orcid.org/0000-0003-1039-5264 Qiu Yunping yunping.qiu@einstein.yu.edu 3 Weiss Louis M. louis.weiss@einstein.yu.edu 3 4 https://orcid.org/0000-0003-3541-779X Nagajyothi Jyothi F. jfn31@njms.rutgers.edu 1 Silva Marcos Vinícius 1 Department of Microbiology Biochemistry and Molecular Genetics Public Health Research Institute New Jersey Medical School Newark USA phri.org 2 Laboratory of Cell-Cell Interactions Instituto de Ciências Biológicas Departamento de Morfologia Belo Horizonte Brazil icb.ufmg.br 3 Department of Medicine Albert Einstein College of Medicine New York USA yu.edu 4 Department of Pathology Albert Einstein College of Medicine New York USA yu.edu 2019 20 12 2019 2019 10 07 2019 21 08 2019 20 12 2019 2019 Copyright © 2019 Kezia Lizardo et al. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Chagas disease is caused by Trypanosoma cruzi which is endemic in Latin America. T. cruzi infection results in a latent infection with approximately a third of latently infected patients developing chronic Chagas cardiomyopathy (CCM). CCM is a common cause of cardiomyopathy in endemic regions and has a poor prognosis compared to other cardiomyopathies. The factors responsible for the transition from the asymptomatic indeterminate latent stage of infection to CCM are poorly understood. Our previous studies demonstrated that lipid metabolism and diet are important determinants of disease progression. In the present study, we analyzed various serum metabolomic biomarkers such as acylcarnitines, amino acids, biogenic amines, glycerophospholipids, and sphingolipids in murine models of CCM, where the mice specifically develop either left or right ventricular cardiomyopathy based on the diets fed during the indeterminate stage in a murine model of Chagas disease. Our data provide new insights into the metabolic changes that may predispose patients to CCM and biomarkers that may help predict the risk of developing cardiomyopathy from T. cruzi infection. Author Summary . Chronic Chagas cardiomyopathy (CCM) is a parasitic disease prevalent in Latin America. Currently, no effective drugs or vaccines are available to prevent or cure CCM. The factors involved in the disease severity and progression are poorly understood to design new therapeutic interventions. In order to rapidly identify Chagas patients with a higher risk to develop CCM, a new set of biomarkers specific to Chagas disease is needed. We performed serum metabolomic analyses in chronic T. cruzi -infected mice fed on different diets and identified cardiac ventricular-specific metabolite biomarkers that could define CCM severity. In this paper, we present the results of serum metabolomic analyses and discuss its correlations to the diet-induced metabolic regulations in the pathogenesis of CCM in a murine model of Chagas disease. National Cancer Institute P60DK020541 National Institutes of Health HL-122866
Publisher Copyright:
© 2019 Kezia Lizardo et al.
PY - 2019
Y1 - 2019
N2 - Chagas disease is caused by Trypanosoma cruzi which is endemic in Latin America. T. cruzi infection results in a latent infection with approximately a third of latently infected patients developing chronic Chagas cardiomyopathy (CCM). CCM is a common cause of cardiomyopathy in endemic regions and has a poor prognosis compared to other cardiomyopathies. The factors responsible for the transition from the asymptomatic indeterminate latent stage of infection to CCM are poorly understood. Our previous studies demonstrated that lipid metabolism and diet are important determinants of disease progression. In the present study, we analyzed various serum metabolomic biomarkers such as acylcarnitines, amino acids, biogenic amines, glycerophospholipids, and sphingolipids in murine models of CCM, where the mice specifically develop either left or right ventricular cardiomyopathy based on the diets fed during the indeterminate stage in a murine model of Chagas disease. Our data provide new insights into the metabolic changes that may predispose patients to CCM and biomarkers that may help predict the risk of developing cardiomyopathy from T. cruzi infection. Author Summary. Chronic Chagas cardiomyopathy (CCM) is a parasitic disease prevalent in Latin America. Currently, no effective drugs or vaccines are available to prevent or cure CCM. The factors involved in the disease severity and progression are poorly understood to design new therapeutic interventions. In order to rapidly identify Chagas patients with a higher risk to develop CCM, a new set of biomarkers specific to Chagas disease is needed. We performed serum metabolomic analyses in chronic T. cruzi-infected mice fed on different diets and identified cardiac ventricular-specific metabolite biomarkers that could define CCM severity. In this paper, we present the results of serum metabolomic analyses and discuss its correlations to the diet-induced metabolic regulations in the pathogenesis of CCM in a murine model of Chagas disease.
AB - Chagas disease is caused by Trypanosoma cruzi which is endemic in Latin America. T. cruzi infection results in a latent infection with approximately a third of latently infected patients developing chronic Chagas cardiomyopathy (CCM). CCM is a common cause of cardiomyopathy in endemic regions and has a poor prognosis compared to other cardiomyopathies. The factors responsible for the transition from the asymptomatic indeterminate latent stage of infection to CCM are poorly understood. Our previous studies demonstrated that lipid metabolism and diet are important determinants of disease progression. In the present study, we analyzed various serum metabolomic biomarkers such as acylcarnitines, amino acids, biogenic amines, glycerophospholipids, and sphingolipids in murine models of CCM, where the mice specifically develop either left or right ventricular cardiomyopathy based on the diets fed during the indeterminate stage in a murine model of Chagas disease. Our data provide new insights into the metabolic changes that may predispose patients to CCM and biomarkers that may help predict the risk of developing cardiomyopathy from T. cruzi infection. Author Summary. Chronic Chagas cardiomyopathy (CCM) is a parasitic disease prevalent in Latin America. Currently, no effective drugs or vaccines are available to prevent or cure CCM. The factors involved in the disease severity and progression are poorly understood to design new therapeutic interventions. In order to rapidly identify Chagas patients with a higher risk to develop CCM, a new set of biomarkers specific to Chagas disease is needed. We performed serum metabolomic analyses in chronic T. cruzi-infected mice fed on different diets and identified cardiac ventricular-specific metabolite biomarkers that could define CCM severity. In this paper, we present the results of serum metabolomic analyses and discuss its correlations to the diet-induced metabolic regulations in the pathogenesis of CCM in a murine model of Chagas disease.
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U2 - 10.1155/2019/4956016
DO - 10.1155/2019/4956016
M3 - Article
C2 - 31949545
AN - SCOPUS:85077442147
VL - 2019
JO - Disease Markers
JF - Disease Markers
SN - 0278-0240
M1 - 4956016
ER -