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Pathogens
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Metabolic Dysfunction in Chagas Cardiomyopathy
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Metabolic Dysfunction in Chagas Cardiomyopathy

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Parasitic Pathogens".

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 9104

Special Issue Editor

Dr. Jyothi F Nagajyothi

E-Mail Website
Guest Editor
Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, USA
Interests: adipocytes; adipose tissue; infectious diseases; HIV; parasite; COVID-19; tuberculosis; inflammation; metabolism

Special Issue Information

Dear Colleagues,

Chagas disease (CD) is a neglected tropical disease caused by the parasite Trypanosoma cruzi. Approximately 8 million people in Latin America are chronically infected with T. cruzi, and 65–100 million people are living in areas at risk for infection worldwide. Among them, up to 30% develop debilitating and life-threatening symptomatic chronic chagasic cardiomyopathy (CCC). There is a serious knowledge gap in understanding the basis for transition from asymptomatic to symptomatic CCC. Currently, no effective drugs or vaccines exist to prevent or cure CCC. CCC has been mostly studied as an immunological disease, with the last several decades of investigations focused on the roles of inflammatory pathways in CCC pathogenesis. Recently, it has been concluded that the mechanisms underlying the development and progression of CCC are complex and multifactorial, yet the role of cardiac metabolism in the pathogenesis of CCC is still poorly understood. For this Special Issue of Pathogens, we invite you to submit research articles, review articles, short notes, and communications related to molecular and cellular metabolic dysfunctions in the heart, host metabolic deregulation, and immunometabolic alterations in Chagas disease. We look forward to your contribution.

Asso. Prof. Jyothi F Nagajyothi
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Trypanosoma cruzi
  • Chagas cardiomyopathy
  • Cardiac/serum metabolism
  • Lipid metabolism
  • Metabolic stress
  • Oxidative and ER stress
  • Animal models
  • Chagas patients

Published Papers (2 papers)

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Research

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20 pages, 2160 KiB  
Article
Functional Autoreactive Anti-β2 Adrenergic Antibodies May Contribute to Insulin Resistance Profile in Patients with Chronic Chagas Disease
by Luz María Rodeles, Miguel Hernán Vicco, Álvaro Siano, Leonardo Andrés Fuchs, Luz María Peverengo, Silvia Sanchez Puch, Cora Beatriz Cymeryng, Iván Sergio Marcipar and Pablo Arias
Pathogens 2021, 10(3), 378; https://doi.org/10.3390/pathogens10030378 - 21 Mar 2021
Viewed by 2643
Abstract
Potential activation of β2 adrenergic receptors (β2AR) by specific autoreactive antibodies (Abs) that arise during the host reaction to Trypanosoma cruzi, could contribute to the elevated prevalence of metabolic disturbances described in patients with chronic Chagas disease (CCD). This study aimed to [...] Read more.
Potential activation of β2 adrenergic receptors (β2AR) by specific autoreactive antibodies (Abs) that arise during the host reaction to Trypanosoma cruzi, could contribute to the elevated prevalence of metabolic disturbances described in patients with chronic Chagas disease (CCD). This study aimed to determine the prevalence of anti-β2AR Abs in patients with CCD, as well as the correlation of these Abs with the presence of glucose and lipid metabolism disturbances, in order to explore their association with an insulin resistance profile. Additionally, we tested the functional effects of anti-β2AR Abs employing an in vitro bioassay with neuroendocrine cells expressing β2AR. A clinical and metabolic evaluation including an OGTT was performed in 80 CCD patients and 40 controls. Anti-β2AR Abs were measured by an in-house-developed ELISA, and the β2 adrenergic activity of affinity-purified IgG fractions from patient’ sera were assayed in CRE-Luc and POMCLuc transfected AtT-20 cells. A higher proportion of dysglycemia (72.5% vs. 37.5%; p = 0.001) was observed in the CCD group, accompanied by increased HOMA2-IR (p = 0.019), especially in subjects with Abs (+). Anti-β2AR Abs reactivity (7.01 (2.39–20.5); p = 0.0004) and age >50 years (3.83 (1.30–11.25); p = 0.014) resulted as relevant for IR prediction (AUC: 0.786). Concordantly, Abs (+) CCD patients showed elevated metabolic risk scores and an increased prevalence of atherogenic dyslipidemia (p = 0.040), as compared to Abs (−) patients and controls. On functional bioassays, Abs exerted specific and dose-dependent β2-agonist effects. Our findings suggest that anti-β2AR Abs may induce the activation of β2AR in other tissues besides the heart; furthermore, we show that in patients with CCD these Abs are associated with an insulin resistance profile and atherogenic dyslipidemia, providing biological plausibility to the hypothesis that adrenergic activation by anti-β2AR Abs could contribute to the pathogenesis of metabolic disturbances described in CCD patients, increasing their cardiovascular risk. Full article
(This article belongs to the Special Issue Metabolic Dysfunction in Chagas Cardiomyopathy)
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Review

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26 pages, 1997 KiB  
Review
Chagas Cardiomyopathy: From Romaña Sign to Heart Failure and Sudden Cardiac Death
by Antonia Pino-Marín, Germán José Medina-Rincón, Sebastian Gallo-Bernal, Alejandro Duran-Crane, Álvaro Ignacio Arango Duque, María Juliana Rodríguez, Ramón Medina-Mur, Frida T. Manrique, Julian F. Forero and Hector M. Medina
Pathogens 2021, 10(5), 505; https://doi.org/10.3390/pathogens10050505 - 22 Apr 2021
Cited by 17 | Viewed by 6042
Abstract
Despite nearly a century of research and accounting for the highest disease burden of any parasitic disease in the Western Hemisphere, Chagas disease (CD) is still a challenging diagnosis, primarily due to its poor recognition outside of Latin America. Although initially considered endemic [...] Read more.
Despite nearly a century of research and accounting for the highest disease burden of any parasitic disease in the Western Hemisphere, Chagas disease (CD) is still a challenging diagnosis, primarily due to its poor recognition outside of Latin America. Although initially considered endemic to Central and South America, globalization, urbanization, and increased migration have spread the disease worldwide in the last few years, making it a significant public health threat. The international medical community’s apparent lack of interest in this disease that was previously thought to be geographically restricted has delayed research on the complex host–parasite relationship that determines myocardial involvement and its differential behavior from other forms of cardiomyopathy, particularly regarding treatment strategies. Multiple cellular and molecular mechanisms that contribute to degenerative, inflammatory, and fibrotic myocardial responses have been identified and warrant further research to expand the therapeutic arsenal and impact the high burden attributed to CD. Altogether, cardiac dysautonomia, microvascular disturbances, parasite-mediated myocardial damage, and chronic immune-mediated injury are responsible for the disease’s clinical manifestations, ranging from asymptomatic disease to severe cardiac and gastrointestinal involvement. It is crucial for healthcare workers to better understand CD transmission and disease dynamics, including its behavior on both its acute and chronic phases, to make adequate and evidence-based decisions regarding the disease. This review aims to summarize the most recent information on the epidemiology, pathogenesis, clinical presentation, diagnosis, screening, and treatment of CD, emphasizing on Chagasic cardiomyopathy’s (Ch-CMP) clinical presentation and pathobiological mechanisms leading to sudden cardiac death. Full article
(This article belongs to the Special Issue Metabolic Dysfunction in Chagas Cardiomyopathy)
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