Kamel Fatemah O, Mahjoub S K, Ahmad M A A Sattar, Jamal Maha H, Bakhshwin Duaa M, Burzangi Abdulhadi S, Shaker Soad, Magadmi Rania
Department of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Anatomy Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Front Pharmacol. 2025 Apr 28;16:1573332. doi: 10.3389/fphar.2025.1573332. eCollection 2025.
Vitamin D is essential for calcium-phosphorus homeostasis, skeletal mineralization, and cardiovascular health. Its deficiency is associated with increased risk of metabolic syndrome and cardiovascular diseases. In this study, we aimed to investigate the relationship between vitamin D deficiency and cardiovascular metabolic syndrome while identifying underlying mechanisms.
Forty-eight Wistar albino rats were divided into four groups: control, vitamin D deficient (VD-), metabolic syndrome (MetS), and combined vitamin D deficient with metabolic syndrome (VD- + MetS). VD- and VD- + MetS rats were fed a vitamin D-deficient diet with increased calcium and phosphate to prevent secondary hyperparathyroidism and to determine the direct effects of vitamin D. Metabolic syndrome was induced 10% fructose in drinking water for 8 weeks. Evaluations included metabolic syndrome markers (hypertension, diabetes, dyslipidemia, and obesity), myocardial injury indicators (lactate dehydrogenase [LDH] and creatine kinase-MB [CK-MB]), and oxidative stress/inflammation markers (malondialdehyde [MDA] and nitric oxide [NO]). Vascular reactivity in thoracic aorta tissues, heart weight, and histopathological changes were also assessed.
The results revealed that vitamin D deficiency was strongly related to each component of metabolic syndrome. Combined vitamin D deficiency and metabolic syndrome induced a highly significant increase in CK-MB, LDH, NO, and MDA levels (p < 0.05). However, there was no significant difference in CK-MB and NO levels for the (VD-) group compared to the control (p > 0.05). Heart weight was significantly increased, and a histological examination of the heart showed increased left ventricular and aortic wall thickness in the combined group (p < 0.05). Vascular response to phenylephrine was significantly increased, whereas the vascular response to acetylcholine was significantly decreased in all experimental groups (VD-, MetS, and VD- + MetS) compared to control (p < 0.05).
The present study demonstrates that vitamin D deficiency is considered one of the major risky and predisposing factors for cardiovascular metabolic syndrome, which could affect the outcome of the disease, partly by affecting endothelial function, vascular oxidative stress, and inflammation.
维生素D对于钙磷稳态、骨骼矿化以及心血管健康至关重要。其缺乏与代谢综合征和心血管疾病风险增加相关。在本研究中，我们旨在调查维生素D缺乏与心血管代谢综合征之间的关系，并确定潜在机制。
48只Wistar白化大鼠被分为四组：对照组、维生素D缺乏组（VD-）、代谢综合征组（MetS）以及维生素D缺乏合并代谢综合征组（VD- + MetS）。给VD-组和VD- + MetS组大鼠喂食维生素D缺乏饮食，并增加钙和磷的含量，以预防继发性甲状旁腺功能亢进，并确定维生素D的直接作用。通过在饮水中添加10%果糖诱导代谢综合征8周。评估指标包括代谢综合征标志物（高血压、糖尿病、血脂异常和肥胖）、心肌损伤指标（乳酸脱氢酶[LDH]和肌酸激酶同工酶MB[CK-MB]）以及氧化应激/炎症标志物（丙二醛[MDA]和一氧化氮[NO]）。还评估了胸主动脉组织的血管反应性、心脏重量和组织病理学变化。
结果显示，维生素D缺乏与代谢综合征的各个组成部分密切相关。维生素D缺乏合并代谢综合征导致CK-MB、LDH、NO和MDA水平显著升高（p < 0.05）。然而，与对照组相比，VD-组的CK-MB和NO水平无显著差异（p > 0.05）。心脏重量显著增加，对心脏的组织学检查显示，合并组的左心室和主动脉壁厚度增加（p < 0.05）。与对照组相比，所有实验组（VD-、MetS和VD- + MetS）对去氧肾上腺素的血管反应显著增加，而对乙酰胆碱的血管反应显著降低（p < 0.05）。
本研究表明，维生素D缺乏被认为是心血管代谢综合征的主要危险因素和易感因素之一，它可能部分通过影响内皮功能、血管氧化应激和炎症来影响疾病的结局。
