Vitamin D attenuates pro-inflammatory TNF-α cytokine expression by inhibiting NF-кB/p65 signaling in hypertrophied rat hearts

Abstract

A growing body of evidence suggests that immune activation and inflammatory mediators may play a key role in the development and progression of left ventricle (LV) hypertrophy. The present study was designed to test the hypothesis that the cardioprotective effect of cholecalciferol (Vit-D3) is mediated via the regulation of messenger RNA (mRNA) expression of pro-inflammatory cytokines. Rats were randomly divided into four groups: control group received normal saline (0.9 % NaCl) i.p. for 14 days; Vit-D3 group received Vit-D3 at a dose of 12 μg/kg/day by gavage for 14 days; ISO group received saline for 7 days, and at day 7, ISO (5 mg/kg/day) was injected i.p. for 7 consecutive days to induce cardiac hypertrophy; and Vit-D3 + ISO group was treated with Vit-D3 for 14 days, and at day 7, ISO was administered for 7 consecutive days. Heart/body weight ratio, troponin-T, creatine kinase-MB, and tumor necrosis factor-α (TNF-α) levels of LV tissue were estimated. Levels of mRNA expression of NF-кB (NF-кB)/p65 and inhibitory kappa B (IкB)-α were determined by real-time PCR. Vit-D3 administration before and during induction of cardiac hypertrophy significantly reduced (P < 0.001) cardiac biomarkers. The histopathological examination further confirmed these results. In addition, Vit-D3 significantly decreased (P < 0.001) NF-кB-p65 mRNA expression and increased (P < 0.01) IкB-α mRNA expression in LV tissues compared to ISO group. Based on these findings, it was concluded that the administration of cholecalciferol markedly attenuated the development of ISO-induced cardiac hypertrophy likely through downregulation of TNF-α /NF-кb/p65 signaling pathways. However, it should be pointed out that other signaling pathways may contribute to the cardioprotective effect of Vit-D3 which requires further investigation.

The Effects of Vitamin D Supplementation on Biomarkers of Inflammation and Oxidative Stress in Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…Previous studies showed that vitamin D intake might reduce inflammatory factors by inhibiting the production of IL-6 [37,38]. Moreover, vitamin D may inhibit the nuclear factor κB (NF-κB) activity by increasing the expression of IκB, which in turn would result in a significant decrease in the production of pro-inflammatory factors, such as IL-8 [39]. Our meta-analysis of RCTs showed that vitamin D supplementation resulted in a significant increase in TAC and GSH, and a significant decrease in MDA levels in diabetics.…”

Mechanisms of Action of Vitamin D as Supplemental Therapy for Pneumocystis Pneumonia

“…Vitamin D has been shown to reduce the expression of TNF-␣ by decreasing NF-B-p65 mRNA expression and increasing IB-␣ mRNA expression (9). In a recent study of 118 women, those who were deficient in vitamin D had higher serum levels of TNF-␣ (10).…”

Role of Vitamin D in Cardiovascular Diseases

“…Diabetes, a chronic inflammatory disease, is a risk factor for LVH [30]. Reversal of LVH in diabetic rats [31] and attenuation of TNF-α expression by inhibition of nuclear factor-kappa beta (NF-κB/p65) signaling in hypertrophied rat hearts with vitamin D [32] suggest the role of vitamin D in reversal of LVH. These studies suggest a pathogenic role of vitamin D deficiency in LVH and vitamin D supplementation is cardioprotective.…”