Department of Nutrition and Food Hygiene, School of Public Health, Dalian Medical University, Dalian 116044, China; Department of Cardiology, Institute of Cardiovascular Diseases, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
School of Public Health, Dalian Medical University, Dalian 116044, China.
J Steroid Biochem Mol Biol. 2018 Apr;178:293-302. doi: 10.1016/j.jsbmb.2018.01.009. Epub 2018 Jan 11.
Vitamin D (VD) and its analogues play critical roles in metabolic and cardiovascular diseases. Recent studies have demonstrated that VD exerts a protective role in cardiovascular diseases. However, the beneficial effect of VD on pressure overload-induced cardiac remodeling and dysfunction and its underlying mechanisms are not fully elucidated. In this study, cardiac dysfunction and hypertrophic remodeling in mice were induced by pressure overload. Cardiac function was evaluated by echocardiography, and myocardial histology was detected by H&E and Masson's trichrome staining. Cardiomyocyte size was detected by wheat germ agglutinin staining. The protein levels of signaling mediators were examined by western blotting while mRNA expression of hypertrophic and fibrotic markers was examined by qPCR analysis. Oxidative stress was detected by dihydroethidine staining. Our results showed that administration of VD3 significantly ameliorates pressure overload-induced contractile dysfunction, cardiac hypertrophy, fibrosis and inflammation in mice. In addition, VD3 treatment also markedly inhibited cardiac oxidative stress and apoptosis. Moreover, protein levels of calcineurin A, ERK1/2, AKT, TGF-β, GRP78, cATF6, and CHOP were significantly reduced whereas SERCA2 level was upregulated in the VD3-treated hearts compared with control. These results suggest that VD3 attenuates cardiac remodeling and dysfunction induced by pressure overload, and this protective effect is associated with inhibition of multiple signaling pathways.
维生素 D（VD）及其类似物在代谢和心血管疾病中发挥着关键作用。最近的研究表明，VD 在心血管疾病中具有保护作用。然而，VD 对压力超负荷诱导的心脏重构和功能障碍的有益作用及其潜在机制尚未完全阐明。在这项研究中，通过压力超负荷诱导小鼠出现心脏功能障碍和肥大重构。通过超声心动图评估心脏功能，通过 H&E 和 Masson 三色染色检测心肌组织学，通过小麦胚凝集素染色检测心肌细胞大小。通过 Western blot 检测信号转导介质的蛋白水平，通过 qPCR 分析检测肥大和纤维化标志物的 mRNA 表达。通过二氢乙啶染色检测氧化应激。我们的结果表明，VD3 的给药可显著改善压力超负荷诱导的小鼠收缩功能障碍、心脏肥大、纤维化和炎症。此外，VD3 治疗还显著抑制心脏氧化应激和细胞凋亡。此外，与对照组相比，VD3 处理的心脏中钙调神经磷酸酶 A、ERK1/2、AKT、TGF-β、GRP78、cATF6 和 CHOP 的蛋白水平显著降低，而 SERCA2 水平上调。这些结果表明，VD3 可减轻压力超负荷诱导的心脏重构和功能障碍，这种保护作用与抑制多种信号通路有关。
