Developments in the management of Chagas cardiomyopathy

Tanowitz, Herbert B.; Machado, Fabiana S.; Spray, David C.; Friedman, Joel M.; Weiss, Oren S; Lora, Jose N; Nagajyothi, Jyothi F.; Moraes, Diego N; Garg, Nisha; Nunes, Maria Carmo Pereira; Ribeiro, Antônio Luiz Pinho

doi:10.1586/14779072.2015.1103648

Cited by 69 publications

(63 citation statements)

References 185 publications

(230 reference statements)

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“…Currently, treatments for Chagas disease are based on benznidazole (12). This drug is effective and well tolerated in children and during the acute phase; however, its clinical efficacy is inadequate for treating the chronic form of the illness due to its low efficacy, association with severe adverse events, and the fact that it does not modify the course of the disease (13).…”

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confidence: 99%

Simvastatin Attenuates Endothelial Activation through 15-Epi-Lipoxin A4 Production in Murine Chronic Chagas Cardiomyopathy

González‐Herrera

Cramer

Pimentel

et al. 2017

Antimicrob Agents Chemother

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Current treatments for chronic Chagas cardiomyopathy, a disease with high mortality rates and caused by the protozoan Trypanosoma cruzi, are unsatisfactory. Myocardial inflammation, including endothelial activation, is responsible for the structural and functional damage seen in the chronic phase. The clinical efficacy of benznidazole could be improved by decreasing chronic inflammation. Statins, which have anti-inflammatory properties, may improve the action of benznidazole. Here, the action of simvastatin in a murine model of chronic Chagas cardiomyopathy and the link with the production of the proresolving eicosanoid 15-epi-lipoxin A4, produced by 5-lipoxygenase, are evaluated. Simvastatin decreased the expression of the adhesion molecules E-selectin, intracellular adhesion molecule type 1 (ICAM-1), and vascular cell adhesion molecule type 1 (VCAM-1) in T. cruzi-infected mice. However, when this drug was administered to 5-lipoxygenase-deficient mice, the antiinflammatory effect was not observed unless exogenous 15-epi-lipoxin A4 was administered. Thus, in chronic Chagas disease, 5-epi-lipoxin A4 induced by simvastatin treatment could improve the pathophysiological condition of patients by increasing the trypanocidal action of benznidazole.

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mentioning

confidence: 99%

Simvastatin Attenuates Endothelial Activation through 15-Epi-Lipoxin A4 Production in Murine Chronic Chagas Cardiomyopathy

González‐Herrera

Cramer

Pimentel

et al. 2017

Antimicrob Agents Chemother

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“…It was described in 1909 by the Brazilian physician Carlos Chagas and affects millions of people worldwide, especially in Latin America. One of the most important clinical manifestations is chagasic cardiomyopathy, which is observed in acute and chronic symptomatic patients [1]. In about 30% of the chronic patients, electrocardiographic (ECG) abnormalities, such as arrhythmias and atrioventricular blockade; lymphoid inflammatory infiltration, fibrosis, cardiac damage are observed [2,3].…”

Section: Introductionmentioning

confidence: 99%

Rapamycin Treatment Reduces Acute Myocarditis Induced by <b><i>Trypanosoma cruzi</i></b> Infection

et al. 2019

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Chagas disease affects millions of people mainly in Latin America and is a protozoan illness caused by the parasite Trypanosoma cruzi. Chagasic cardiomyopathy is the leading cause of mortality of infected patients, due to compromised electrical and mechanical cardiac function induced by tissue remodeling, especially fibrosis, and lymphocytic infiltration. Some cellular biochemical pathways can be protective to the heart, and we tested if the in vivo activation of the autophagic machinery by rapamycin could reduce parasite-induced myocarditis. Regarding the expression of LC3, an autophagy marker, we observed its upregulation in the cardiac tissue of infected untreated mice. However, after rapamycin treatment, an autophagy inducer, infected mice showed reduced electrical cardiac dysfunctions, myocarditis, cardiac damage, and reduced production of pro-inflammatory cytokines by the heart. On the other hand, the parasite's life cycle was not affected, and we observed no modulations in cardiac tissue or blood parasitemia. Our data indicate that, at least partially, autophagy induction controls inflammation in the heart¸ illustrating the complexity of the pathways that concur to the development of the infection.

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“…Most individuals that progress to chronic phase remain asymptomatic, and the disease is detected by serological tests, but no clinical, radiologic, electrocardiographic, or echocardiographic evidenced. Overall, 20-40% of asymptomatic individuals develop clinically relevant Chagas heart disease, while approximately 10% of the cases progress to digestive problems [14,15]. In fact, the disease outcome toward differential clinical forms is related to many factors including the host-parasite interaction.…”

Section: Chagas Disease: An Outburst Of Inflammatory Events That May mentioning

confidence: 99%

Physiology and Pathology of Infectious Diseases: The Autoimmune Hypothesis of Chagas Disease

Mattoso-Barbosa¹,

Sathler-Avelar²,

Coelho-dos-Reis³

et al. 2017

Physiology and Pathology of Immunology

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Infectious pathologies are a group of diseases that contribute with great impact on public health worldwide. Among the various diseases, some have a higher epidemiological importance, since their morbidity and mortality are very significant. In addition to the usual immune response, mounted against noxious agents, there is still the concept of infection-induced autoimmunity. Autoimmune diseases are defined as illnesses in which the evolution from benign to pathogenic autoimmunity takes place. However, proving a disease to be of autoimmune etiology is not a simple task. It is well known that both genetic influences and environmental factors trigger autoimmune disorders. However, some theories are still under great discussion. One of the most intriguing self-induced disorders is the hypothesis of autoimmunity during Chagas disease. Since the mid-1970s, the Chagas autoimmunity hypothesis has been considered an important contributor to the complex immune response developed by the host and triggered by Trypanosoma cruzi. New ideas and findings have strengthened this hypothesis, which has been reported in a series of publications from different groups around the world. The aim of this chapter is to discuss the mechanisms involving autoimmunity development during Chagas disease.

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Developments in the management of Chagas cardiomyopathy

Cited by 69 publications

References 185 publications

Simvastatin Attenuates Endothelial Activation through 15-Epi-Lipoxin A4 Production in Murine Chronic Chagas Cardiomyopathy

Simvastatin Attenuates Endothelial Activation through 15-Epi-Lipoxin A4 Production in Murine Chronic Chagas Cardiomyopathy

Rapamycin Treatment Reduces Acute Myocarditis Induced by <b><i>Trypanosoma cruzi</i></b> Infection

Physiology and Pathology of Infectious Diseases: The Autoimmune Hypothesis of Chagas Disease

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