Unveiling the molecular Culprit of arterial stiffness in vitamin D deficiency and obesity: Potential for novel therapeutic targets
Adel B. Elmoselhi,
Amal Bouzid,
Mohamed Seif Allah,
Zeinab Ibrahim,
Khuloud Bajbouj,
Rebal S. Abou Assaleh,
Thenmozhi Venkatachalam,
Mohamed Madkour,
Ruqaiyyah Siddiqui,
Naveed Ahmed Khan,
Rifat A. Hamoudi
Affiliations
Adel B. Elmoselhi
College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates; Corresponding author. P.O. 27272, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
Amal Bouzid
Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
Mohamed Seif Allah
College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates; Cardiology Department, University Hospital Sharjah, United Arab Emirates
Zeinab Ibrahim
Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
Khuloud Bajbouj
College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
Rebal S. Abou Assaleh
Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
Thenmozhi Venkatachalam
Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
Mohamed Madkour
Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
Ruqaiyyah Siddiqui
College of Arts and Sciences, American University of Sharjah, University City, Sharjah 26666, United Arab Emirates; Department of Medical Biology, Faculty of Medicine, Istinye University, Istanbul, 34010, Turkey
Naveed Ahmed Khan
College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates; Department of Medical Biology, Faculty of Medicine, Istinye University, Istanbul, 34010, Turkey
Rifat A. Hamoudi
College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates; Division of Surgery and Interventional Science, University College London, London, United Kingdom; ASPIRE Precision Medicine Research Institute Abu Dhabi, University of Sharjah, Sharjah, United Arab Emirates
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.