Identifying Molecular Mechanisms and Biomarkers for Arterial Stiffness in Vitamin D Deficiency, Obese, and Diabetic Patients

Background and Aims: Patients who suffer from vitamin D3 deficiency, obesity, and diabetes mellitus (DM) are at higher risk of cardiovascular diseases (CVDs). Arterial stiffness is also shown to be increased and linked with those patients. In this study, we intended to identify circulating MicroRNAs (miRNAs) biomarkers and explore molecular mechanisms of arterial stiffness in those patients as early predictors of CVDs. Methods and Results: Twenty-three adult Emiratis patients were recruited and divided in the following groups: A control healthy group with vitamin D ≥ 20ng, and BMI ≤ 30 (C1 group =11 individuals); a second group with vitamin D deficiency (Vit D level ≤ 20 ng) and obesity (BMI ≥ 30) (A1 group = 9 patients); and a third group with vitamin D deficiency, obesity, plus Diabetes Mellitus (DM) (A2 group = 3 patients). Pulse wave velocity (PWV) was measured and the whole transcriptome analysis with qPCR validation for miRNA in plasma samples were tested. PWV relative to age was significantly higher in A1 and A2 groups 19.4 ± 4.7 m/s and 18.3 ± 1.3 m/s respectively, compared to the control group 14.7 ± 2.1 m/s (p < 0.05). Whole RNA-Sequencing revealed miR-182-5p; miR-199a-5p; miR-193a-5p; and miR-155-5p were differentially over-expressed (logFC > 1.5) in A1 and A2 groups. Additionally, the expression of the following oxidative stress and inflammatory biomarkers were significantly (p <0.05) higher in the A1 group vs C1 group: HIF-1alpha, NOX-I, NOX-II, cytokine IL-1b, IL-6, IL-8, IL-10, and VEGF. Conclusion: We identify 4 miRNAs for arterial stiffness in patients with vitamin D deficiency, obesity and DM. Furthermore, several oxidative stress and inflammatory genes and biomarkers seem to underlie the culprits of arterial stiffness in vitamin D deficiency and obese patients. Those biomarkers could serve as diagnostic and therapeutic targets for the early prevention of CVDs. Sheikh Hamdan Bin Rashid Al Maktoum Award for Medical Sciences, Ref: MRG/38, and Targeted Research Grant from University of Sharjah, Office of Research and Graduate Studies. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.