Department of Surgery, University of Rochester Medical Center, Rochester, NY, USA.
Arterioscler Thromb Vasc Biol. 2013 Aug;33(8):1960-4. doi: 10.1161/ATVBAHA.113.301843. Epub 2013 Jun 13.
To determine the role of patched receptor (Ptc)-1 in mediating pulsatile flow-induced changes in vascular smooth muscle cell growth and vascular remodeling.
In vitro, human coronary arterial smooth muscle cells were exposed to normal or pathological low pulsatile flow conditions for 24 hours using a perfused transcapillary flow system. Low pulsatile flow increased vascular smooth muscle cell proliferation when compared with normal flow conditions. Inhibition of Ptc-1 by cyclopamine attenuated low flow-induced increases in Notch expression while concomitantly decreasing human coronary arterial smooth muscle cell growth to that similar under normal flow conditions. In vivo, ligation injury-induced low flow increased vascular smooth muscle cell growth and vascular remodeling, while increasing Ptc-1/Notch expression. Perivascular delivery of Ptc-1 small interfering RNA by pluronic gel inhibited the pathological low flow-induced increases in Ptc-1/Notch expression and markedly reduced the subsequent vascular remodeling.
These results suggest that pathological low flow stimulates smooth muscle cell growth in vitro and vascular remodeling in vivo via Ptc-1 regulation of Notch signaling.
确定 patched 受体（Ptc）-1 在介导搏动流诱导的血管平滑肌细胞生长和血管重塑变化中的作用。
在体外，使用灌注跨毛细血管流动系统将人冠状动脉平滑肌细胞暴露于正常或病理低搏动流条件下 24 小时。与正常流条件相比，低搏动流增加了血管平滑肌细胞的增殖。用环巴胺抑制 Ptc-1 可减弱低流诱导的 Notch 表达增加，同时使人类冠状动脉平滑肌细胞生长降低至类似于正常流条件下的水平。在体内，结扎损伤诱导的低流增加了血管平滑肌细胞的生长和血管重塑，同时增加了 Ptc-1/Notch 的表达。多聚物凝胶通过血管周 delivery 给予 Ptc-1 小干扰 RNA 抑制了病理性低流诱导的 Ptc-1/Notch 表达增加，并显著减少了随后的血管重塑。
这些结果表明，病理性低流通过 Ptc-1 调节 Notch 信号刺激体外平滑肌细胞生长和体内血管重塑。
