Netrin-1 is associated with macrophage infiltration and polarization in human epicardial adipose tissue in coronary artery disease

Abstract Background Inflammatory activity originating from the epicardial adipose tissue (EAT) may have a role in coronary artery disease (CAD) pathogenesis. The relationship between macrophage infiltration, polarization in the EAT, and netrin-1 gene expression was investigated. Methods Macrophage i...

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Bibliographic Details
Published in:Journal of cardiology 2017-06, Vol.69 (6), p.851-858
Main Authors: Gurses, Kadri Murat, MD, PhD, Ozmen, Fusun, MD, PhD, Kocyigit, Duygu, MD, Yersal, Nilgun, MSc, Bilgic, Elif, MD, Kaya, Erkan, MD, Kopru, Cagla Zubeyde, PhD, Soyal, Tolga, MD, Doganci, Suat, MD, Tokgozoglu, Lale, MD, Korkusuz, Petek, MD, PhD
Format: Article
Language:English
Subjects:
Adipose Tissue - immunology
Adipose Tissue - metabolism
Aged
Cardiovascular
Coronary Artery Bypass
Coronary artery disease
Coronary Artery Disease - genetics
Coronary Artery Disease - immunology
Coronary Artery Disease - surgery
Epicardial adipose tissue
Female
Gene Expression
Humans
Interleukin-12 - genetics
Interleukin-18 - genetics
Macrophage polarization
Macrophages - immunology
Male
Middle Aged
Nerve Growth Factors - genetics
Netrin-1
Pericardium - immunology
Pericardium - metabolism
Receptors, Cell Surface - genetics
Tumor Suppressor Proteins - genetics
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Summary:Abstract Background Inflammatory activity originating from the epicardial adipose tissue (EAT) may have a role in coronary artery disease (CAD) pathogenesis. The relationship between macrophage infiltration, polarization in the EAT, and netrin-1 gene expression was investigated. Methods Macrophage infiltration and polarization were examined by immunohistochemical methods and expression levels of netrin-1 , Unc5b , and cytokines related with M1-macrophage subtype (IL-12 and IL-18) were determined by quantitative polymerase chain reaction in subcutaneous and epicardial adipose tissue obtained from patients undergoing coronary artery bypass grafting and non-coronary cardiac surgery. Results CAD patients had higher CD68+ ( p = 0.005) and CD11c+ ( p < 0.001) macrophage count in EAT when compared to the controls. CD11c+/CD206+ macrophage ratio, which reflects dominancy of M1-macrophage phenotype, was significantly increased in EAT of CAD patients when compared to that of the controls ( p = 0.008). CAD patients had significantly higher netrin-1 , Unc5b , and IL-18 gene expression in the EAT when compared to the control group ( p < 0.001, p < 0.001, and p = 0.006 respectively). Increased macrophage infiltration and polarization were associated with higher netrin-1 , Unc5b , and IL-12 gene expression in EAT ( p < 0.05). Conclusions Findings suggest a link between enhanced netrin-1 expression in EAT and macrophage infiltration and polarization in patients with CAD.
ISSN:0914-5087
1876-4738
DOI:10.1016/j.jjcc.2016.08.016