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

Endocr Metab Immune Disord Drug Targets. 2018;18(5):522-529. doi: 10.2174/1871530318666180426101756.


Background: The exact mechanisms underlying the protective effect of vitamin D in the pathogenesis of atherosclerosis and coronary heart disease are 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). Compared 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 antiatherosclerotic effect of vitamin D is at least partly attributed to the up-regulation of anti-inflammatory cytokines especially TGF- β1.

Keywords: CAD patients; IL-35; TGF-β; coronary angiography; coronary artery disease; serum cytokines; vitamin D..

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / immunology
  • Cross-Sectional Studies
  • Female
  • Humans
  • Interleukin-12 Subunit p35 / blood*
  • Male
  • Middle Aged
  • Severity of Illness Index
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*
  • Transforming Growth Factor beta1 / blood*
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D Deficiency / blood*
  • Vitamin D Deficiency / diagnosis
  • Vitamin D Deficiency / immunology


  • Biomarkers
  • IL12A protein, human
  • Interleukin-12 Subunit p35
  • TGFB1 protein, human
  • Transforming Growth Factor beta1
  • Vitamin D
  • 25-hydroxyvitamin D