Xu Wei, Hu Xiao, Qi Xi, Zhu Rui, Li Chen, Zhu Yanjing, Yin Shuai, Cheng Liming, Zhu Rongrong
Division of Spine, Department of Orthopedics, Tongji Hospital affiliated to Tongji University School of Medicine, Shanghai, China.
Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration, Tongji University, Ministry of Education, Shanghai, China.
J Vasc Res. 2019;56(1):17-27. doi: 10.1159/000496164. Epub 2019 Mar 15.
Vitamin D has an important protective effect on chronic inflammatory disease. Angiotensin II (AngII) triggers vascular damage and plays a key role in vascular diseases via several mechanisms, including inflammation. Conversely, vitamin D has been shown to have an important protective effect on chronic inflammation. There is evidence showing that vitamin D can reverse the effects of AngII, but the molecular mechanisms by which this occurs are not known. Our results demonstrate that vitamin D improved the viability, migration ability, and tube formation of AngII-pretreated endothelial progenitor cells (EPCs) and inhibited the apoptosis of EPCs induced by AngII. Vitamin D also reversed reactive oxygen species production, vascular inflammatory cytokine generation, and nuclear factor kappa-B activation in EPCs induced by AngII. Furthermore, EPC pretreatment with GW9662 (the antagonist for PPAR-γ) or siHO-1 decreased the protective effect of vitamin D on AngII-induced EPC injury. Overall, our data indicate that vitamin D ameliorated AngII-induced abnormal EPC injury by decreasing oxidative stress and inflammatory cytokine levels. These findings also suggest that vitamin D protected EPCs from AngII-induced vascular injury via the activation of the PPAR-γ/HO-1 signaling pathway.
维生素D对慢性炎症性疾病具有重要的保护作用。血管紧张素II（AngII）通过多种机制引发血管损伤并在血管疾病中起关键作用，包括炎症。相反，维生素D已被证明对慢性炎症具有重要的保护作用。有证据表明维生素D可以逆转AngII的作用，但其发生的分子机制尚不清楚。我们的结果表明，维生素D改善了经AngII预处理的内皮祖细胞（EPCs）的活力、迁移能力和成管能力，并抑制了AngII诱导的EPCs凋亡。维生素D还逆转了AngII诱导的EPCs中活性氧的产生、血管炎性细胞因子的生成以及核因子κB的激活。此外，用GW9662（PPAR-γ拮抗剂）或siHO-1预处理EPCs可降低维生素D对AngII诱导的EPC损伤的保护作用。总体而言，我们的数据表明，维生素D通过降低氧化应激和炎性细胞因子水平改善了AngII诱导的EPC异常损伤。这些发现还表明，维生素D通过激活PPAR-γ/HO-1信号通路保护EPCs免受AngII诱导的血管损伤。
