Dysregulation of Autonomic Nervous System in Chagas' Heart Disease Is Associated with Altered Adipocytokines Levels

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2015 Jul 7

PMID 26147101

Citations 10

Authors

Joao Marcos Barbosa-Ferreira

Charles Mady

Barbara Maria Ianni

Heno Ferreira Lopes

Felix Jose Alvarez Ramires

Vera Maria Cury Salemi

Cesar Jose Grupi

Denise Tessariol Hachul

Fabio Fernandes

Affiliations

Soon will be listed here.

Abstract

Background: Chagas disease (CD) induces autonomic dysfunction and inflammatory activity, which may promote metabolic abnormalities. We studied metabolism and his correlation with Autonomic Nervous System (ANS) and inflammation in CD.

Methods And Results: Sixty subjects were divided into 4 groups: control group (CG), IF (indeterminate form) group; ECG group (ECG abnormalities and normal left ventricular systolic function), and LVD group (left ventricular sistolic dysfunction). Levels of adiponectin, leptin, insulin, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) were assayed in serum samples by ELISA. ANS was assessed by heart rate variability in frequency domain in 24-hour Holter and postural tilt test (rest and orthostatic position). High frequency (HFr) component values were used to estimate parasympathetic activity and low frequency (LFr) component, sympathetic activity. Analyzes were made of the correlations of each of the metabolic parameters (leptin and adiponectin) with the inflammatory cytokines (interleukin-6 and TNF- alpha) and with the ANS assessment measurements. No significant differences were observed in leptin and insulin levels. Adiponectin was higher in ECG and LVD groups: [CG = 4766.5 (5529.5), IF = 4003.5 (2482.5), ECG = 8376.5 (8388.5), LVD = 8798 (4188.0) ng/mL, p<0.001)]. IL-6 and TNF-alpha were higher in LVD group: [IL-6: CG = 1.85 (6.41); IF = 1.58 (1.91); ECG = 1.0 (1.57); LVD= 31.44 (72.19) pg/ml; p = 0.001. TNF-alpha: CG = 22.57 (88.2); IF = 19.31 (33.16); ECG = 12.45 (3.07); LVD = 75.15 (278.57) pg/ml; p = 0.04]. Adiponectin levels had a positive association with the HFr component (r = 0.539; p = 0.038) and an inverse association with the LFr component (r = - 0.539; p = 0.038) in ECG group. Leptin levels had a negative association with the HFr component (r= - 0.632; p = 0.011) and a positive association with the LFr component (r = 0.632; p = 0.011) in LVD group.

Conclusions: We found increased adiponectin levels in Chagas' heart disease with systolic dysfunction and in patients with ECG abnormalities and normal systolic function at rest. Adipocytokines levels (adiponectin and leptin) were associated with ANS parameters in Chagas' heart disease.

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References

Combs T, Nagajyothi , Mukherjee S, de Almeida C, Jelicks L, Schubert W . The adipocyte as an important target cell for Trypanosoma cruzi infection. J Biol Chem. 2005; 280(25):24085-94. DOI: 10.1074/jbc.M412802200. View

. Research priorities for Chagas disease, human African trypanosomiasis and leishmaniasis. World Health Organ Tech Rep Ser. 2013; (975):v-xii, 1-100. View

Ferreira A, Segatto M, Menezes Z, Macedo A, Gelape C, Oliveira Andrade L . Evidence for Trypanosoma cruzi in adipose tissue in human chronic Chagas disease. Microbes Infect. 2011; 13(12-13):1002-5. PMC: 3552247. DOI: 10.1016/j.micinf.2011.06.002. View

Fu M, Zhou J, Qian J, Jin X, Zhu H, Zhong C . Adiponectin through its biphasic serum level is a useful biomarker during transition from diastolic dysfunction to systolic dysfunction - an experimental study. Lipids Health Dis. 2012; 11:106. PMC: 3492043. DOI: 10.1186/1476-511X-11-106. View

Oliveira L, Juliano Y, Novo N, Neves M . Blood glucose and insulin response to intravenous glucose by patients with chronic Chagas' disease and alcoholism. Braz J Med Biol Res. 1993; 26(11):1187-90. View

Fernandes F, Dantas S, Ianni B, Ramires F, Buck P, Salemi V . Leptin levels in different forms of Chagas' disease. Braz J Med Biol Res. 2007; 40(12):1631-6. DOI: 10.1590/s0100-879x2006005000152. View

Ianni B, Arteaga E, Frimm C, Pereira Barretto A, Mady C . Chagas' heart disease: evolutive evaluation of electrocardiographic and echocardiographic parameters in patients with the indeterminate form. Arq Bras Cardiol. 2001; 77(1):59-62. DOI: 10.1590/s0066-782x2001000700006. View

Gascon J, Bern C, Pinazo M . Chagas disease in Spain, the United States and other non-endemic countries. Acta Trop. 2009; 115(1-2):22-7. DOI: 10.1016/j.actatropica.2009.07.019. View

Fasshauer M, Klein J, Neumann S, Eszlinger M, Paschke R . Adiponectin gene expression is inhibited by beta-adrenergic stimulation via protein kinase A in 3T3-L1 adipocytes. FEBS Lett. 2001; 507(2):142-6. DOI: 10.1016/s0014-5793(01)02960-x. View

10.

Paolisso G, Manzella D, Montano N, Gambardella A, Varricchio M . Plasma leptin concentrations and cardiac autonomic nervous system in healthy subjects with different body weights. J Clin Endocrinol Metab. 2000; 85(5):1810-4. DOI: 10.1210/jcem.85.5.6511. View

11.

Berg A, Scherer P . Adipose tissue, inflammation, and cardiovascular disease. Circ Res. 2005; 96(9):939-49. DOI: 10.1161/01.RES.0000163635.62927.34. View

12.

Guariento M, Saad M, Muscelli E, Gontijo J . Heterogenous insulin response to an oral glucose load by patients with the indeterminate clinical form of Chagas' disease. Braz J Med Biol Res. 1993; 26(5):491-5. View

13.

Nagajyothi F, Desruisseaux M, Thiruvur N, Weiss L, Braunstein V, Albanese C . Trypanosoma cruzi infection of cultured adipocytes results in an inflammatory phenotype. Obesity (Silver Spring). 2009; 16(9):1992-7. PMC: 2771879. DOI: 10.1038/oby.2008.331. View

14.

Antoniades C, Antonopoulos A, Tousoulis D, Stefanadis C . Adiponectin: from obesity to cardiovascular disease. Obes Rev. 2009; 10(3):269-79. DOI: 10.1111/j.1467-789X.2009.00571.x. View

15.

Marin-Neto J, Cunha-Neto E, Maciel B, Simoes M . Pathogenesis of chronic Chagas heart disease. Circulation. 2007; 115(9):1109-23. DOI: 10.1161/CIRCULATIONAHA.106.624296. View

16.

Prata A . Clinical and epidemiological aspects of Chagas disease. Lancet Infect Dis. 2002; 1(2):92-100. DOI: 10.1016/S1473-3099(01)00065-2. View

17.

Trayhurn P, Duncan J, Hoggard N, Rayner D . Regulation of leptin production: a dominant role for the sympathetic nervous system?. Proc Nutr Soc. 1998; 57(3):413-9. DOI: 10.1079/pns19980060. View

18.

Ribeiro A, Moraes R, Ribeiro J, Ferlin E, Torres R, Oliveira E . Parasympathetic dysautonomia precedes left ventricular systolic dysfunction in Chagas disease. Am Heart J. 2001; 141(2):260-5. DOI: 10.1067/mhj.2001.111406. View

19.

Nagajyothi F, Kuliawat R, Kusminski C, Machado F, Desruisseaux M, Zhao D . Alterations in glucose homeostasis in a murine model of Chagas disease. Am J Pathol. 2013; 182(3):886-94. PMC: 3586686. DOI: 10.1016/j.ajpath.2012.11.027. View

20.

Wakabayashi S, Aso Y . Adiponectin concentrations in sera from patients with type 2 diabetes are negatively associated with sympathovagal balance as evaluated by power spectral analysis of heart rate variation. Diabetes Care. 2004; 27(10):2392-7. DOI: 10.2337/diacare.27.10.2392. View