• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>American Journal of Physiology >Effects of D-4F on vasodilation, oxidative stress, angiostatin, myocardial inflammation, and angiogenic potential in tight-skin mice.
【24h】

Effects of D-4F on vasodilation, oxidative stress, angiostatin, myocardial inflammation, and angiogenic potential in tight-skin mice.

机译：D-4F对紧肤小鼠血管舒张，氧化应激，血管抑素，心肌炎症和血管生成潜能的影响。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Systemic sclerosis (scleroderma, SSc) is an autoimmune, connective tissue disorder that is characterized by impaired vascular function, increased oxidative stress, inflammation of internal organs, and impaired angiogenesis. Tight skin mice (Tsk(-/+)) have a defect in fibrillin-1, resulting in replication of many of the myocardial and vascular features seen in humans with SSc. D-4F is an apolipoprotein A-I (apoA-I) mimetic that improves vascular function in diverse diseases such as hypercholesterolemia, influenza, and sickle cell disease. Tsk(-/+) mice were treated with either phosphate-buffered saline (PBS) or D-4F (1 mg.kg(-1).day(-1) for 6-8 wk). Acetylcholine and flow-induced vasodilation were examined in facialis arteries. Proinflammatory HDL (p-HDL) in murine and human plasma samples was determined by the cell-free assay. Angiostatin levels in murine and human plasma samples were determined by Western blot analysis. Hearts were examined for changes in angiostatin and autoantibodies against oxidized phosphotidylcholine (ox-PC). Angiogenic potential in thin sections of murine hearts was assessed by an in vitro vascular endothelial growth factor (VEGF)-induced endothelial cell (EC) tube formation assay. D-4F improved endothelium-, endothelial nitric oxide synthase-dependent, and flow-mediated vasodilation in Tsk(-/+) mice. Tsk(-/+) mice had higher plasma p-HDL and angiostatin levels than C57BL/6 mice, as did SSc patients compared with healthy control subjects. Tsk(-/+) mice also had higher triglycerides than C57BL/6 mice. D-4F reduced p-HDL, angiostatin, and triglycerides in the plasma of Tsk(-/+) mice. Tsk(-/+) hearts contained notably higher levels of angiostatin and autoantibodies against ox-PC than those of control hearts. D-4F ablated angiostatin in Tsk(-/+) hearts and reduced autoantibodies against ox-PC by >50% when compared with hearts from untreated Tsk(-/+) mice. Angiogenic potential in Tsk(-/+) hearts was increased only when the Tsk(-/+) mice were treated with D-4F (1 mg.kg(-1).day(-1),6-8 wk), and cultured sections of hearts from the D-4F-treated Tsk(-/+) mice were incubated with D-4F (10 microg/ml, 5-7 days). Failure to treat the thin sections of hearts and Tsk(-/+) mice with D-4F resulted in loss of VEGF-induced EC tube formation. D-4F improves vascular function, decreases myocardial inflammation, and restores angiogenic potential in the hearts of Tsk(-/+) mice. As SSc patients have increased plasma p-HDL and angiostatin levels similar to the Tsk(-/+) mice, D-4F may be effective at treating vascular complications in patients with SSc.
机译：系统性硬化症（硬皮病，SSc）是一种自身免疫性结缔组织疾病，其特征是血管功能受损，氧化应激增加，内部器官发炎和血管生成受损。紧密的皮肤小鼠（Tsk（-/ +））在fibrillin-1中存在缺陷，导致在患有SSc的人中见到许多心肌和血管特征的复制。 D-4F是一种载脂蛋白A-I（apoA-I）模拟物，可改善多种疾病（例如高胆固醇血症，流感和镰状细胞病）中的血管功能。 Tsk（-/ +）小鼠用磷酸盐缓冲盐水（PBS）或D-4F（1 mg.kg（-1）.day（-1）进行6-8周的治疗）。在面动脉中检查乙酰胆碱和血流诱导的血管舒张。通过无细胞测定法测定鼠和人血浆样品中的促炎性HDL（p-HDL）。通过蛋白质印迹分析确定鼠和人血浆样品中的血管抑制素水平。检查心脏中血管抑制素和抗氧化磷脂酰胆碱（ox-PC）自身抗体的变化。通过体外血管内皮生长因子（VEGF）诱导的内皮细胞（EC）管形成分析评估了小鼠心脏薄片中的血管生成潜力。 D-4F改善了Tsk（-/ +）小鼠中的内皮依赖性，内皮型一氧化氮合酶依赖性和血流介导的血管舒张。与健康对照组相比，Tsc（-/ +）小鼠的血浆p-HDL和血管抑制素水平高于C57BL / 6小鼠，SSc患者也是如此。 Tsk（-/ +）小鼠的甘油三酸酯也比C57BL / 6小鼠高。 D-4F减少了Tsk（-/ +）小鼠血浆中的p-HDL，血管抑制素和甘油三酸酯。与对照心脏相比，Tsk（-/ +）心脏所含的血管抑制素和针对ox-PC的自身抗体水平明显更高。与未经治疗的Tsk（-/ +）小鼠的心脏相比，D-4F消融了Tsk（-/ +）心脏中的血管抑制素，并将针对ox-PC的自身抗体降低了50％以上。仅当用D-4F（1 mg.kg（-1）.day（-1），6-8 wk）处理Tsk（-/ +）小鼠时，Tsk（-/ +）心脏中的血管生成潜力才增加。将经D-4F处理的Tsk（-/ +）小鼠的心脏培养切片与D-4F（10 microg / ml，5-7天）一起孵育。无法用D-4F治疗心脏和Tsk（-/ +）小鼠的薄切片导致VEGF诱导的EC管形成的丧失。 D-4F可改善Tsk（-/ +）小鼠心脏的血管功能，减少心肌炎症并恢复血管生成潜能。由于SSc患者的血浆p-HDL和血管抑制素水平与Tsk（-/ +）小鼠相似，因此D-4F可能有效治疗SSc患者的血管并发症。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号