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Original article
DOI: 10.1016/j.rec.2019.07.005
Available online 7 September 2019
Interleukin-5 levels are decreased in the plasma of coronary artery disease patients and inhibit Th1 and Th17 differentiation in vitro
Los niveles de interleucina-5 disminuyen en plasma de pacientes con enfermedad coronaria e inhiben la diferenciación in vitro de Th1 y Th17
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Di Yea,b,c,, Zhen Wanga,b,c,, Jing Yea,b,c,, Menglong Wanga,b,c,, Jianfang Liua,b,c, Yao Xua,b,c, Huimin Jianga,b,c, Jiangbin Chena,b,c, Jun Wana,b,c,
Corresponding author
wanjun@whu.edu.cn

Corresponding author: Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute, 238 Jiefang Road, Wuhan 430060, China.
a Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
b Cardiovascular Research Institute, Wuhan University, Wuhan, China
c Hubei Key Laboratory of Cardiology, Wuhan, China
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Received 05 January 2019. Accepted 12 July 2019
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Table 1. Reverse transcription-quantitative polymerase chain reaction primers used
Table 2. Clinical characteristics in coronary tissue sample donors
Table 3. Clinical characteristics of patients providing blood samples
Table 4. Variables associated with the presence of coronary artery disease
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Abstract
Introduction and objectives

Interleukin (IL)-5 is an anti-inflammatory cytokine that has been demonstrated to be involved in cardiovascular diseases, including aortic aneurysm and heart failure. This study aimed to investigate the involvement of IL-5 in coronary artery disease (CAD) and the possible mechanisms.

Methods

We analyzed IL-5 expression in human coronary artery specimens collected from CAD patients and deceased donors. Plasma IL-5, IL-17, and interferon-γ levels in CAD patients were detected using ELISA kits, with samples from chest pain patients (non-CAD) as controls. Mouse CD4+T helper (Th) cells were separated, and the effect of IL-5 on Th1, regulatory T cell and Th17 differentiation and mRNA levels of their characteristic cytokines were detected using flow cytometry and reverse transcription-quantitative polymerase chain reaction, respectively.

Results

IL-5 was significantly decreased in the coronary plaque of CAD patients compared with the deceased donors group, and IL-5 was mainly derived from macrophages in the coronary artery plaque. Compared with the non-CAD group, plasma IL-5 levels in the CAD groups were significantly lower, and the sequence from high to low was stable angina pectoris, unstable angina pectoris, and acute myocardial infarction. Binary linear regression analysis showed that IL-5 was independently correlated with the occurrence of CAD. Recombinant mouse IL-5 treatment decreased Th1 and Th17 levels and mRNA expression of their characteristic cytokines in oxidized low-density lipoprotein-treated CD4+Th cells.

Conclusion

IL-5 levels were decreased in CAD patients and inhibited oxidized low-density lipoprotein Th1 and Th17 differentiation in vitro.

Keywords:
Coronary artery disease
Inflammation
Interleukin-5
Th1 differentiation
Th17 differentiation
Regulatory T cell
Abbreviations:
AMI
CAD
IL-5
SAP
UAP
Resumen
Introducción y objetivos

La interleucina 5 (IL-5) es una citocina antiinflamatoria que se ha involucrado en las enfermedades cardiovasculares, incluidos los aneurismas aórticos y la insuficiencia cardiaca. El objetivo de este estudio es investigar el papel de la IL-5 en la enfermedad coronaria (EC) y sus posibles mecanismos.

Métodos

Se analizó la expresión de la IL-5 en muestras de arterias coronarias humanas de 17 pacientes con EC y donantes fallecidos. Además, se determinaron las concentraciones plasmáticas de IL-5, IL-17 e interferón gamma en pacientes con EC usando kits ELISA con muestras de pacientes con dolor torácico (sin EC) como controles. Se separaron las células murinas CD4+T helper (Th), y el efecto de la IL-5 en la diferenciación de Th1, célula T reguladora y Th17 y la cantidad de ARNm de sus citocinas características se determinaron mediante citometría de flujo y reacción en cadena de la polimerasa tras transcripción inversa respectivamente.

Resultados

La IL-5 disminuyó significativamente en las placas coronarias de los pacientes con EC comparados con el grupo de donantes fallecidos, y la IL-5 derivó fundamentalmente de los macrófagos de las placas de las arterias coronarias. Además, comparados con el grupo sin EC, las concentraciones plasmáticas de IL-5 en el grupo de EC fueron significativamente menores, y la secuencia de mayor a menor fue angina estable, angina inestable e infarto de miocardio. El análisis de regresión linear binaria mostró que la IL-5 se correlacionó independientemente con la aparición de la EC. Además, el tratamiento con IL-5 recombinante de ratón disminuyó los valores de Th1 y Th17 y la expresión del ARNm de sus citocinas características en lipoproteínas oxidadas de baja densidad tratadas con CD4+Th.

Conclusiones

Los valores de IL-5 disminuyeron en los pacientes con EC e inhiben la diferenciación in vitro de Th1 y Th17 inducida por lipoproteínas oxidadas de baja densidad.

Palabras clave:
Enfermedad coronaria
Inflamación
Interleucina 5
Diferenciación de Th1
Diferenciación de Th17
Célula T reguladora

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