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Randomized Controlled Trial
. 2022 Jun 28;14(13):2683.
doi: 10.3390/nu14132683.

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

Domenico Rendina  1 , Lanfranco D Elia  1 , Veronica Abate  1 , Andrea Rebellato  2 , Ilaria Buondonno  3 , Mariangela Succoio  4 , Fabio Martinelli  4 , Riccardo Muscariello  1 , Gianpaolo De Filippo  5 , Patrizia D Amelio  3   6 , Francesco Fallo  2 , Pasquale Strazzullo  1 , Raffaella Faraonio  4
Affiliations
Randomized Controlled Trial

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

Domenico Rendina et al. Nutrients. .

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.

Keywords: calcitriol; cholecalciferol; clinical trial; hypertension; hypovitaminosis D; inflammation; miR-21.

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Conflict of interest statement

D.R. has previously consulted for Kyowa Kyrin. The other authors declare no conflict of interest. ABIOGEN had no role in the design of the study; in the collection, analyses, or interpretation of the data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Circulating levels of miR-21 and 25OHD in the study cohorts before and after treatment with cholecalciferol or placebo: (a) miR-21 circulating levels in C-cohort HYPODD patients (dark histograms) and in P-cohort HYPODD patients (white histograms) before (T0) and two months (T2) after treatment with cholecalciferol (C-cohort) or with placebo (P-cohort); (b) 25OHD serum levels in C-cohort HYPODD patients (dark histograms) and in P-cohort HYPODD patients (white histograms) before (T0) and two months (T2) after treatment with cholecalciferol (C-cohort) or with placebo (P-cohort).
Figure 2
Figure 2
In vitro effects of 1,25(OH)2D3 treatment on miR-21, vitamin D receptor messenger RNA, and cytochrome P450 family 24 subfamily A member 1 messenger RNA expression levels. Human embryonic kidney (HEK293) cell lines were treated with different concentrations (1 nM, 10 nM, and 100 nM) of 1,25(OH)2D3 for 24 h. (a) Real-time quantitative polymerase chain reaction (RT-qPCR) analyses of miR-21 in HEK293 cells treated with 1,25(OH)2D3. The relative levels of miR-21 were evaluated using as control cells treated with ethanol vehicle control (EtOH) alone. MiR-16 was used as an internal standard for normalization. (b) Single gene expression analysis in HEK 293 cells treated with 1,25(OH)2D3. The relative amounts of vitamin D receptor (VDR) and cytochrome P450 family 24 subfamily A member 1 (CYP24A1) messenger ribonucleic acid (mRNAs) after 1,25(OH)2D3 treatments were evaluated with RT-qPCR using as control EtOH–treated cells. Statistical differences of ΔCt were marked with * standing for p < 0.05 and ** standing for p < 0.01.
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Grants and funding

HYPODD is a no-profit study. The study costs are partially covered by a SIIA research grant 2011 (to L.D.) and by a Società Italiana Osteoporosi, Malattie del Metabolismo Minerale e dello Scheletro (SIOMMMS) research grant 2014 (to R.M.).