Center for Clinical & Translational Science, Creighton University School of Medicine, Omaha, NE 68178, USA.
Exp Mol Pathol. 2012 Aug;93(1):82-90. doi: 10.1016/j.yexmp.2012.04.006. Epub 2012 Apr 17.
Vitamin D is a sectosteroid that functions through Vitamin D receptor (VDR), a transcription factor, which controls the transcription of many targets genes. Vitamin D deficiency has been linked with cardiovascular diseases, including heart failure and coronary artery disease. Suppressor of cytokine signaling (SOCS)3 regulates different biological processes such as inflammation and cellular differentiation and is an endogenous negative regulator of cardiac hypertrophy.
The purpose of this study was to test the hypothesis that vitamin D deficiency causes cardiomyocyte hypertrophy and increased proinflammatory profile in epicardial adipose tissue (EAT), and this correlates with decreased expression of SOCS3 in cardiomyocytes and EAT.
Eight female Yucatan miniswine were fed vitamin D-sufficient (900 IU/d) or vitamin D-deficient hypercholesterolemic diet. Lipid profile, metabolic panel, and serum 25(OH)D levels were regularly measured. After 12 months animals were euthanized and histological, immunohistochemical and qPCR studies were performed on myocardium and epicardial fat.
Histological studies showed cardiac hypertrophy, as judged by cardiac myocyte cross sectional area, in the vitamin D-deficient group. Immunohistochemical and qPCR analyses showed significantly decreased mRNA and protein expression of VDR and SOCS3 in cardiomyocytes of vitamin D-deficient animals. EAT from vitamin D-deficient group had significantly higher expression of TNF-α, IL-6, MCP-1, and decreased adiponectin in association with increased inflammatory cellular infiltrate. Interestingly, EAT from vitamin D-deficient group had significantly decreased expression of SOCS3.
These data suggest that vitamin D deficiency induces hypertrophy in cardiomyocytes which is associated with decreased expression of VDR and SOCS3. Vitamin D deficiency is also associated with increased inflammatory markers in EAT. Activity of VDR in the body is controlled through regulation of vitamin D metabolites. Therefore, restoration of VDR function by supplementation of VDR ligands in vitamin D-deficient population might be helpful in reducing inflammation and cardiovascular risk.
维生素 D 是一种固醇类激素，通过维生素 D 受体（VDR）发挥作用，VDR 是一种转录因子，可控制许多靶基因的转录。维生素 D 缺乏与心血管疾病有关，包括心力衰竭和冠心病。细胞因子信号转导抑制因子（SOCS）3 调节多种生物学过程，如炎症和细胞分化，是心肌肥厚的内源性负调节剂。
本研究旨在验证假设，即维生素 D 缺乏会导致心肌细胞肥大和心外膜脂肪组织（EAT）中促炎表型增加，并且与心肌细胞和 EAT 中 SOCS3 表达减少相关。
8 只雌性尤卡坦小型猪分别喂食维生素 D 充足（900IU/d）或维生素 D 缺乏的高胆固醇饮食。定期测量血脂谱、代谢组和血清 25（OH）D 水平。12 个月后，处死动物并对心肌和心外膜脂肪进行组织学、免疫组织化学和 qPCR 研究。
组织学研究表明，维生素 D 缺乏组的心肌细胞横截面积增大，提示发生心肌肥大。维生素 D 缺乏动物的心肌细胞中 VDR 和 SOCS3 的 mRNA 和蛋白表达明显降低。维生素 D 缺乏组的 EAT 中 TNF-α、IL-6、MCP-1 表达明显升高，脂联素表达降低，炎症细胞浸润增加。有趣的是，维生素 D 缺乏组的 EAT 中 SOCS3 的表达明显降低。
这些数据表明，维生素 D 缺乏会导致心肌细胞肥大，这与 VDR 和 SOCS3 的表达降低有关。维生素 D 缺乏还与 EAT 中促炎标志物的增加有关。VDR 在体内的活性通过维生素 D 代谢物的调节来控制。因此，在维生素 D 缺乏人群中补充 VDR 配体以恢复 VDR 功能可能有助于降低炎症和心血管风险。
