Inflammatory genes in epicardial fat contiguous with coronary atherosclerosis in the metabolic syndrome and type 2 diabetes: changes associated with pioglitazone

Abstract

Objective: To determine changes in gene expression in epicardial adipose tissue (EAT) associated with coronary atherosclerosis (CAD) and effects of pioglitazone therapy.

Research design and methods: Genes were quantified by RT-PCR in EAT and thoracic subcutaneous adipose tissue (SAT) obtained during surgery in CAD patients with metabolic syndrome (MS) or type 2 diabetes and control subjects with minimal or no CAD and no MS or type 2 diabetes.

Results: Increased expression of interleukin-1 receptor antagonist (IL-1Ra) and IL-10, a trend for higher IL-1β, and no change in peroxisome proliferator-activated receptor-γ (PPARγ) was found in EAT from MS or type 2 diabetes. Only PPARγ mRNA was reduced in SAT. Pioglitazone therapy in type 2 diabetes was associated with decreased expression of IL-1β, IL-1Ra, and IL-10 in EAT; decreased IL-10 in SAT; and increased PPARγ in SAT.

Conclusions: In MS and type 2 diabetes with CAD, proinflammatory and anti-inflammatory genes were differentially increased in EAT and selectively reduced in association with pioglitazone treatment.

Figure 1

IL-1β (A), IL-1Ra (B), IL-10 (C), and PPARγ (D) gene expression in epicardial and sternal subcutaneous fat (SAT) from controls (CON), MS, type 2 diabetic (DM), and type 2 diabetic patients treated with pioglitazone (DM + Pio). The data were normalized by the use of cyclophilin as the recovery standard in each run and shown as the means ± SEM of the ΔCp from cyclophilin, with the sign of the ΔCp values reversed so that the greater the number, the more mRNA. The mean ΔCp values for IL1-β, IL-1Ra, and IL-10 mRNAs assayed in EAT were corrected for the lower recovery of cyclophilin in the MS (0.87 units) and type 2 diabetic (0.81 units) groups. No correction was necessary for SAT, since cyclophilin Cp values in this depot were the same in all groups. Likewise, the cyclophilin Cp values in type 2 diabetic patients without and treated with pioglitazone were not significantly different, being 27.20 ± 0.39 and 27.45 ± 0.40 in SAT and 25.81 ± 0.28 and 25.96 ± 0.34 in EAT, respectively; therefore, no correction factor was necessary. Numbers of patients are shown in brackets. The % changes shown in the figures were derived from the ratios and significant differences in the MS or type 2 diabetic patients compared with control subjects as well as type 2 diabetic patients compared with type 2 diabetic patients treated with pioglitazone and are indicated as follows: *P < 0.05; **P < 0.01; ***P < 0.005. There were no significant differences in expression of the four genes in EAT and SAT between MS and type 2 diabetic patients.