失去ADAMTS5促进了通过versican/integrinβ1/FAK信号的血管化
Zhenyu Zhu1, Hao Liu2, Liyun Feng3
1Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Sino-Japanese Cooperation Platform for Translational Research in Heart Failure, Guangzhou, 510280, PR China; Department of Cardiology, Tongde Hospital of Zhejiang Province, PR China.
溶解蛋白和金属蛋白酶与血栓蛋白动因-5 (ADAMTS5) 缺乏,通过增加versican和激活整合蛋白β1/FAK信号,使血管化恶化. 恢复ADAMTS5可能是血管化的治疗策略.
科学领域:
- 心血管生物学 心血管生物学
- 细胞外矩阵生物学 细胞外矩阵生物学
- 血管病理生理学
背景情况:
- 细胞外矩阵 (ECM) 蛋白酶与血管化病原发生有关.
- 一种带有血栓松丁基因-5 (ADAMTS5) 的分解蛋白和金属蛋白酶重塑了ECM并分裂了versican.
- 在血管化中ADAMTS5的作用尚未完全理解.
研究的目的:
- 研究ADAMTS5在血管化中的调节作用.
- 阐明ADAMTS5,Versican和血管化中的整合素β1/FAK信号之间的机械联系.
主要方法:
- 使用西斑,免疫光和免疫组织化学来评估ADAMTS5的表达.
- 在VSMC和动物模型中进行了ADAMTS5的药理抑制和siRNA淘汰.
- 在各种实验环境中使用了腺病毒介导的ADAMTS5过度表达和抑制.
主要成果:
- 在血管化中,ADAMTS5的表达被下调.
- 阿达姆斯5缺乏症加剧了矿物沉积和大动脉化.
- ADAMTS5过度表达减弱的VSMC和大动脉化.
- 在ADAMTS5调节的Versican水平和整体蛋白β1/FAK信号.
结论:
- 缺少ADAMTS5可促进血管化,通过积和整体蛋白β1/FAK激活.
- ADAMTS5被确定为治疗血管化的潜在治疗标.
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