Vitamin D status in coronary artery disease: association with IL-35 and TGF-β1 and disease severity

BACKGROUND The exact mechanisms underlying the protective effect of vitamin D in the pathogenesis of atherosclerosis and coronary heart disease is obscure. OBJECTIVE Here, we have addressed the relation between vitamin D status and regulatory T cells (Tregs) inhibitory cytokines in patients suffering from coronary artery disease (CAD). MATERIALS AND METHODS 81 patients were divided into single (n= 20), double (n=20) and triple (n=20) vessel disease groups and compared to no vessel disease (No VD) group (n=21). Interleukin (IL) -35 and TGF- β1 were measured using ELISA. Vitamin D was measured using Electrochemiluminescence assay. RESULTS Vitamin D, TGF-β1 and IL-35 concentrations in No VD (32.4±15.2, 667.7±427.6, 12.1±11.9 respectively) group were significantly higher than patients with 1 or more vessel disease (18.1±9.8, 360.4±354.1 and 6.8±8.1 respectively, p<0.05). Subgroup analysis revealed that TGF-β1 and IL-35 (but not vitamin D) were significantly higher in double vessel disease patients (591.9±465.7 and 9.2±8.0 respectively) compared to those with triple vessel disease (173.1±163.3 and 3.6±1.4 respectively, p<0.05). Both TGF-β1 and IL-35 were positively correlated to the serum level of vitamin D (r= 0.38, p= 0.001 and r=0.26, p= 0.028 respectively). Vitamin D, TGF-β1 and IL-35 revealed a negative correlation (r= -0.36, r=-0.46 and r-0.024 respectively) with severity of CAD (p< 0.05). Comparing to normal serum vitamin D patients (326.6±351.7 pg/mL vs. 754.5±560 pg/mL, p=0.036 respectively) TGF-β1 (but not IL-35), was significantly lower in vitamin D deficient patients. CONCLUSION The results suggested that, although decreased TGF-β1 and IL-35 plasma levels correlate positively with decreased vitamin D levels and negatively with severity of CAD, but only TGF-β1 has a significant association with vitamin D deficiency in CAD patients. It seems that the anti-atherosclerotic effect of vitamin D is at least partly attributed to the up-regulation of anti-inflammatory cytokines especially TGF- β1.