在临床和实验性心力衰竭中,失调的骨质保护素/RANK连接体/RANK轴
Thor Ueland1, Arne Yndestad, Erik Øie
1Research Institute for Internal Medicine, Medical Department, Rikshospitalet University Hospital, Oslo, Norway. thor.ueland@medisin.uio.no
Circulation
|May 11, 2005
概括
参与骨代谢的OPG/RANK/RANKL轴与心力衰竭 (HF) 病原发生有关. 这些介质在心脏组织和血清中的表达增加表明它们可能是高血压治疗的治疗标.
科学领域:
- 心血管研究研究心血管研究
- 免疫学 免疫学 免疫学
- 骨的新陈代谢 骨的新陈代谢
背景情况:
- 持续的炎症与心力衰竭 (HF) 的发展有关.
- 骨质保护蛋白 (OPG),RANK和RANKL是TNF超级家族成员,调节骨和免疫反应.
- 研究了OPG/RANK/RANKL轴在HF病原发生中的作用.
研究的目的:
- 调查OPG/RANK/RANKL轴在心力衰竭 (HF) 病原发生过程中的参与.
- 在实验和临床高频模型中探索OPG/RANK/RANKL轴.
主要方法:
- 在老鼠心脏病发作后HF模型中的基因表达分析.
- 在人类HF心肌组织中分析蛋白质水平和免疫组织化学.
- 在人类HF患者中对RANKL和OPG的系统表达分析.
- 在人体纤维细胞中对RANKL对矩阵金属蛋白酶活性的影响的体外研究.
主要成果:
- 增加OPG,RANK和RANKL基因表达在白血病和非白血病心脏组织中的大鼠HF.
- 在人体高血压中心肌蛋白质OPG,RANK和RANKL水平升高,局限于心肌细胞.
- 人类HF中系统RANKL和OPG水平的增加与疾病严重程度相关.
- RANKL增强了矩阵金属蛋白酶活性,这表明它在LV功能障碍中发挥了作用.
结论:
- OPG/RANK/RANKL轴,以骨质平衡而闻名,可能在HF病变发生过程中发挥作用.
- 这些发现确定了心力衰竭的潜在新治疗点.
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