干扰的流动促进动脉硬化通过血栓蛋白-1
Chan Woo Kim1, Anastassia Pokutta-Paskaleva1, Sandeep Kumar1
1From Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta (C.W.K., A.P.-P., S.K., D.-W.K., J.R., R.L.G., H.J., L.P.B.); Department of Microbiology, College of Medicine, Inha University, Incheon, Republic of Korea (C.W.K.); Department of Surgery, Emory University, Atlanta, GA (A.P.-P., A.D.M., T.C., K.M.K., H.L., L.P.B.); Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA (L.H.T.); Department of Bioengineering, University of Utah, Salt Lake City (L.H.T.); Mercer University School of Medicine, Macon, GA (S.D.); Life Science Center, Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki, Japan (H.Y.); George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta (R.L.G.); Surgical and Research Services, Atlanta VA Medical Center, Decatur, GA (L.P.B.); and Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta (L.P.B.).
干扰的流量 (d-流) 通过增加原沉积而导致动脉硬化,而TSP-1则会激活转化生长因子-β通路. 针对TSP-1可能为动脉硬化提供新疗法.
科学领域:
- 心血管生物学
- 生物医学工程
- 翻译医学
背景情况:
- 动脉硬是心血管风险的一个关键因素,与死亡率的增加有关.
- 由低和振荡式剪切应力特征的干扰流 (d-流) 促进动脉样硬化重塑,但其在动脉硬化中的作用尚不清楚.
研究的目的:
- 调查d-流动在动脉硬化中的作用.
- 确定参与d流引起的动脉硬的信号通路.
主要方法:
- 用机械测试和超声波测量动脉硬度.
- 进行了基因表达和通路分析,并进行了体外和体内验证.
- 来自d流和稳定流区域的人类动脉被分析以验证结果.
主要成果:
- 通过原沉积引起了显著的动脉硬,
- 通过激活增长因子-β (TGF-β) 途径,Thrombospondin-1 (TSP-1) 调解了硬化.
- 在TSP-1淘汰的小鼠中,d-流引起的硬化减少;暴露于d-流的人类动脉中,TSP-1和原表达增加.
结论:
- 在剪切介导的动脉硬化中,TSP-1起着至关重要的作用.
- 针对TSP-1及其相关的益纤维路径为d流条件下的动脉硬化提供了潜在的治疗策略.
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