Circulating Levels of IL-35 and Gene Expression of FoxP3 in Coronary Artery Disease: Is There Any Interplay Between Them and 25-Hydroxyvitamin D3?

BACKGROUND: We aimed to evaluate interleukin-35 (IL-35) serum levels and the forkhead box P3 (FoxP3) expression in peripheral blood mononuclear cells (PBMCs) of coronary artery disease (CAD) patients compared with the non-CAD group. Also, we examined the possible relationship between gene expression of FoxP3 and serum levels of IL-35 with several CAD-related clinical parameters. METHODS: This study was conducted on 40 men with CAD and 40 men with a normal coronary artery. The gene expression of FoxP3 was measured by real-time polymerase chain reaction (real-time PCR). The serum concentrations of IL-35 and 25-hydroxyvitamin D3 (25(OH)D3) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: FoxP3 gene expression was significantly decreased in patients compared to controls (p = 0.01). Serum concentrations of IL-35 and 25(OH)D3 were significantly reduced in patients in comparison with the control group (both, p < 0.001), and reduction of IL-35 showed an independent association with CAD. IL-35 levels had a significant positive correlation with serum 25(OH)D3 (r = 0.266, p = 0.044) in the whole population. Moreover, there was an inverse correlation between the FoxP3 expression and CAD severity in CAD patients (r = -0.372, p = 0.01). CONCLUSIONS: It appears that reduced mRNA expression of FoxP3 and circulating level of IL-35 are of significance in the context of CAD pathogenesis. However, more studies are required to elucidate underlying mechanisms.

Niemann-Pick Disease, Type C1 Gene Expression in PBMCs is Associated with Interleukin 10 Serum Concentration: a Case-Control Study.

BACKGROUND: Recent studies showed that atherosclerosis is a lysosomal storage disease (LSD) and Niemann-Pick disease type C1 (NPC1) is the most important protein of the lysosomal membrane that is involved in the removal of FC from lysosomes. Whereas several in vitro and in vivo studies have described the crosstalk between lysosomal cholesterol accumulation and increased inflammation, there is no study addressing the correlation between NPC1 gene expression and an anti-inflammatory cytokine, interleukin 10 (IL-10) serum concentration in atherosclerotic patients. METHODS: IL-10 and 25-hydroxyvitamin D serum concentrations were quantified by enzyme-linked immunosorbent assay (ELISA) in atherosclerotic patients (n = 40) and a control group (n = 40). NPC1 gene expression analysis was performed by quantitative real-time PCR, and correlation between the two parameters was assessed. RESULTS: Mean IL-10 serum concentration and peripheral blood mononuclear cells' (PBMCs) gene expression of NPC1, adjusted for drug consumption, age, and BMI, was not significantly different between the patient and control groups (p = 0.6 and 0.67 respectively). However, NPC1 gene expression showed positive significant correlation with IL-10 serum concentration (p = 0.04, r = 0.29). We also observed lower serum concentration of IL-10 in the subjects with lower 25-hydroxyvitamin D serum concentration (p = 0.034). CONCLUSIONS: Our findings supported the previous observations showing the contribution of lysosomal lipid homeostasis of PBMCs to inflammation and pathogenesis of atherosclerosis.