Vitamin D Status, Cardiovascular Risk Profile, and miRNA-21 Levels in Hypertensive Patients: Results of the HYPODD Study

Abstract

The vitamin D and microRNA (miR) systems may play a role in the pathogenesis of cardiometabolic disorders, including hypertension. The HYPODD study was a double-blind placebo-controlled trial aiming to assess the effects of cholecalciferol treatment in patients with well-controlled hypertension and hypovitaminosis D (25OHD levels < 50 nmol/L). In addition to this clinical trial, we also evaluated the effects of cholecalciferol and calcitriol treatment on miR-21 expression in vivo and in vitro, respectively. Changes in the cardiovascular risk profiles were evaluated in HYPODD patients treated with cholecalciferol (C-cohort) or with placebo (P-cohort). The miR-21circulating levels were measured in four C-cohort patients and five P-cohort patients. In vitro, the miR-21 levels were measured in HEK-293 cells treated with calcitriol or with ethanol vehicle control. Cholecalciferol treatment increased 25OHD levels and reduced parathormone, total cholesterol, and low-density lipoprotein cholesterol levels in C-cohort patients, whereas no significant changes in these parameters were observed in P-cohort patients. The miR-21 circulating levels did not change in the C- or the P-cohort patients upon treatment. Calcitriol treatment did not affect miR-21 levels in HEK-293 cells. In conclusion, hypovitaminosis D correction ameliorated the cardiovascular risk profiles in hypertensive patients treated with cholecalciferol but did not influence the miR-21 expression.

Effect of Vitamin D supplementation on blood pressure in hypertensive individuals with hypovitaminosis D: a systematic review and meta-analysis

“…Dosages of vitamin D used were different from 8000 to 1800 000 UI in total in study. Nine RCTs reported improvement in SBP [25][26][27][28][29][30][31][32][33] and seven in DBP [25,[27][28][29][31][32][33] with supplementation of vitamin D.…”

“…The Cochrane bias evaluation was performed to evaluate study and reporting quality, which are summarized in Table 2. Ten studies provided comprehensive explanations of random sequence generation [25,26,[28][29][30][33][34][35][36][37]. Only one study had a high risk of bias regarding allocation concealment [31].…”

Targeting inflammation in hypertension

“…Conversely, not all markers can be taken as prognostic markers despite of being associated with cardiovascular diseases. For example, miRNA-21, which has been shown to be increased in patients with hypertension and high cardiovascular risk, did not change despite a reduction in cardiovascular risk in patients after correction of hypovitaminosis D [43]. This demonstrates that thorough selection of markers is needed for precise prognosis of disease development in patients with hypertension.…”

Dietary Epigenetic Modulators: Unravelling the Still-Controversial Benefits of miRNAs in Nutrition and Disease

“…Vitamin D3 assumption determined an increase in tumor suppressors miR-100 and miR-125b in both pathological and healthy prostatic tissue [ 118 ]. The HYPODD study correlated the vitamin D supplementation to miR-21 circulating levels in the pathogenesis of cardiometabolic disorders [ 151 ]. Hypovitaminosis D correction (50,000 UI/week for 8 weeks and then 50,000 UI/month for 10 months) ameliorated the cardiovascular risk profiles in hypertensive patients without affecting the miR-21 circulating expression ( Table 1 ) [ 151 ].…”

“…The HYPODD study correlated the vitamin D supplementation to miR-21 circulating levels in the pathogenesis of cardiometabolic disorders [ 151 ]. Hypovitaminosis D correction (50,000 UI/week for 8 weeks and then 50,000 UI/month for 10 months) ameliorated the cardiovascular risk profiles in hypertensive patients without affecting the miR-21 circulating expression ( Table 1 ) [ 151 ]. The effects of 4-week time-restricted eating (TRE), a popular form of intermittent fasting, determined downregulation of a miRNA panel (miR-4649-5p, miR-2467-3p, miR-543, miR-301a-3p, miR-3132, miR-19a-5p, miR-495-3p, and miR-4761-3p), which, in turn, could inhibit cell growth pathways while activating cell survival and promoting healthy aging (NCT03590847) [ 152 ].…”