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Coronary disease is not associated with robust alterations in inflammatory gene expression in human epicardial fat
Timothy P. Fitzgibbons, Nancy Lee, Khanh-Van Tran, Sara Nicoloro, Mark Kelly, Stanley K.C. Tam, Michael P. Czech
Timothy P. Fitzgibbons, Nancy Lee, Khanh-Van Tran, Sara Nicoloro, Mark Kelly, Stanley K.C. Tam, Michael P. Czech
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Research Article Cardiology Inflammation

Coronary disease is not associated with robust alterations in inflammatory gene expression in human epicardial fat

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Abstract

Epicardial adipose tissue (EAT) is the visceral fat depot of the heart. Inflammation of EAT is thought to contribute to coronary artery disease (CAD). Therefore, we hypothesized that the EAT of patients with CAD would have increased inflammatory gene expression compared with controls without CAD. Cardiac surgery patients with (n = 13) or without CAD (n = 13) were consented, and samples of EAT and subcutaneous adipose tissue (SAT) were obtained. Transcriptomic analysis was performed using Affymetrix Human Gene 1.0 ST arrays. Differential expression was defined as a 1.5-fold change (ANOVA P < 0.05). Six hundred ninety-three genes were differentially expressed between SAT and EAT in controls and 805 in cases. Expression of 326 genes was different between EAT of cases and controls; expression of 14 genes was increased in cases, while 312 were increased in controls. Quantitative reverse transcription PCR confirmed that there was no difference in expression of CCL2, CCR2, TNF-α, IL-6, IL-8, and PAI1 between groups. Immunohistochemistry showed more macrophages in EAT than SAT, but there was no difference in their number or activation state between groups. In contrast to prior studies, we did not find increased inflammatory gene expression in the EAT of patients with CAD. We conclude that the specific adipose tissue depot, rather than CAD status, is responsible for the majority of differential gene expression.

Authors

Timothy P. Fitzgibbons, Nancy Lee, Khanh-Van Tran, Sara Nicoloro, Mark Kelly, Stanley K.C. Tam, Michael P. Czech

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Figure 6

qRT-PCR verifies downregulation of NR4A1, NR4A2, and NR4A3 in EAT of cases.

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qRT-PCR verifies downregulation of NR4A1, NR4A2, and NR4A3 in EAT of cas...
(A) INTLN1 expression was greater in EAT than SAT in both cases and controls. (B) NNAT expression was greater in SAT than EAT in both cases and controls. (C) NR4A1 expression was significantly decreased in EAT of cases compared with controls. (D) NR4A2 expression was reduced in EAT of cases in comparison with all other depots. (E) NR4A3 expression was reduced in EAT of cases in comparison with SAT of cases and EAT of controls. (F) SOCS3 expression was increased in the SAT of cases compared with other groups. (G) PTGS2 expression was increased in the SAT of cases compared with EAT. (H) CCR2 expression was not different between groups. (I) CCL2 expression was not different between groups. (J) IL8 expression was not different between groups. (K) IL6 expression was not different between groups. (L) PAI1 expression was not different between groups. (M) TNFA expression was not different between groups (n = 11–12 per group; **P < 0.01, and *P < 0.05 for indicated comparisons using 2-way ANOVA and Tukey’s multiple-comparisons test). In each column, individual subjects are plotted, and error bars show the mean and standard deviation per group. White circles represent controls; black squares represent cases.

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