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Unveiling the molecular Culprit of arterial stiffness in vitamin D deficiency and obesity: Potential for novel therapeutic targets

Elmoselhi, AB; Bouzid, A; Allah, MS; Ibrahim, Z; Bajbouj, K; Abou Assaleh, RS; Venkatachalam, T; ... Hamoudi, RA; + view all (2023) Unveiling the molecular Culprit of arterial stiffness in vitamin D deficiency and obesity: Potential for novel therapeutic targets. Heliyon , 9 (11) , Article e22067. 10.1016/j.heliyon.2023.e22067. Green open access

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Abstract

Cardiovascular diseases (CVDs) are highly associated with both vitamin D deficiency and obesity, two prevalent health conditions worldwide. Arterial stiffness, an independent predictor of CVDs, is particularly elevated in both conditions, yet the molecular mechanisms underlying this phenomenon remain elusive, hindering effective management of CVDs in this population. We recruited 20 middle-aged Emiratis, including 9 individuals with vitamin D deficiency (Vit D level ≤20 ng) and obesity (BMI ≥30) and 11 individuals as control with Vit D level >20 ng and BMI <30. We measured arterial stiffness using pulse wave velocity (PWV) and performed whole transcriptome sequencing to identify differentially expressed genes (DEGs) and enriched pathways. We validated these findings using qRT-PCR, Western blot, and multiplex analysis. PWV was significantly higher in the vitamin D deficient and obese group relative to controls (p ≤ 0.05). The DEG analysis revealed that pathways related to interleukin 1 (IL-1), nitrogen metabolism, HIF-1 signaling, and MAPK signaling were over-activated in the vitamin D deficient and obese group. We found that HIF-1alpha, NOX-I, NOX-II, IL-1b, IL-8, IL-10, and VEGF were significantly upregulated in the vitamin D deficient and obese group (p < 0.05). Our study provides new insights into the molecular mechanisms of arterial stiffness in vitamin D deficiency and obesity, demonstrating the role of oxidative stress and inflammation in this process. Our findings suggest that these biomarkers may serve as potential therapeutic targets for early prevention of CVDs. Further studies are needed to investigate these pathways and biomarkers with larger cohort.

Type: Article
Title: Unveiling the molecular Culprit of arterial stiffness in vitamin D deficiency and obesity: Potential for novel therapeutic targets
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.heliyon.2023.e22067
Publisher version: https://doi.org/10.1016/j.heliyon.2023.e22067
Language: English
Additional information: Copyright © 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: Inflammatory markers, NOX genes, Obesity, Oxidative stress, Vascular dysfunction, Vitamin D
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology
URI: https://discovery.ucl.ac.uk/id/eprint/10184596
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