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Vitamin D intervention does not improve vascular regeneration in diet-induced obese male mice with peripheral ischemia

机译:维生素D干预并未改善饮食诱导的肥胖雄性小鼠的血管再生,外周血缺血

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Vitamin D appears to either promote or inhibit neovascularization in a disease context-dependent manner. The effects of vitamin D, alone or in combination with niacin, on endothelial cell (EC) angiogenic function and on revascularization in obese animals with peripheral ischemia are unknown. Here, we report that supplementation of high palmitate medium with vitamin D, niacin or both vitamins increased EC tube formation, which relies primarily on cell migration, and also maintained tube stability over time. Transcriptomic analyses revealed that both vitamins increased stress response and anti-inflammatory gene expression. However, vitamin D decreased cell cycle gene expression and inhibited proliferation, while niacin induced stable expression of miR-126-3p and -5p and maintained cell proliferation in high palmitate. To assess vascular regeneration, diet-induced obese mice received vitamin D, niacin or both vitamins following hind limb ischemic injury. Niacin, but not vitamin D or combined treatment, improved recovery of hind limb use. Histology of tibialis anterior sections revealed no improvements in revascularization, regeneration, inflammation or fibrosis with vitamin D or combined treatment. In summary, although both vitamin D and niacin increased angiogenic function of EC cultures in high fat, only niacin improved recovery of hind limb use following ischemic injury in obese mice. It is possible that inhibition of cell proliferation by vitamin D in high-fat conditions limits vascular regeneration and recovery from peripheral ischemia in obesity. (C) 2019 The Authors. Published by Elsevier Inc.
机译:维生素D似乎以疾病情境依赖的方式促进或抑制新血管形成。将维生素D,单独或与烟酸组合在内皮细胞(EC)血管生成功能和外周缺血的动物中的血管内容的影响是未知的。在这里,我们报告说,通过维生素D,烟酸或两种维生素增加高棕榈酸盐培养基,增加EC管形成,主要依赖于细胞迁移,并随着时间的推移保持管稳定性。转录组分析显示,既维生素也增加了应激反应和抗炎基因表达。然而,维生素D降低细胞周期基因表达和抑制增殖,而烟酸诱导MiR-126-3P和-5P的稳定表达,并在高棕榈酸盐中保持细胞增殖。为了评估血管再生,饮食诱导的肥胖小鼠接受了后肢缺血性损伤后的维生素D,烟酸或两种维生素。烟酸,但不是维生素D或组合治疗,改善了后肢的恢复。 Tibialis前部的组织学揭示了血运重建,再生,炎症或纤维化的改善,具有维生素D或组合治疗。总之,虽然维生素D和烟酸均增加了高脂肪培养物的血管生成功能,但只有烟酸改善后肢的恢复在肥胖小鼠中缺血性损伤。在高脂肪条件下,维生素D细胞增殖的抑制可能会限制血管再生和从肥胖症中的外周缺血中恢复。 (c)2019年作者。 elsevier公司发布

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