Bettaga Noomen, Jäger Ronald, Dünnes Sarah, Groneberg Dieter, Friebe Andreas
Physiologisches Institut, Universität Würzburg, Röntgenring 9, 97070, Würzburg, Germany.
Angiogenesis. 2015 Jul;18(3):245-54. doi: 10.1007/s10456-015-9463-8. Epub 2015 Mar 21.
Nitric oxide (NO) acts as essential regulator of vasculogenesis and angiogenesis and is critical for arteriogenesis. Whether NO's effects in vivo are mediated through NO-sensitive guanylyl cyclase (NO-GC) and thus by cGMP-dependent mechanisms has been only poorly addressed. Mice lacking NO-GC globally or specifically in smooth muscle cells (SMC) or endothelial cells (EC) were subjected to two established models for arteriogenesis and angiogenesis, namely hindlimb ischemia and oxygen-induced retinopathy. Our data clearly show the involvement of NO-GC in the recovery of blood flow after hindlimb ischemia, and this effect could be attributed to NO-GC in SMC. In the retina, global deletion of NO-GC led to reduced oxygen-induced vessel loss and hypoxia-induced capillary regrowth, whereas pathological neovascularization was increased. These effects were also seen in mice with SMC-specific NO-GC deletion but not in animals lacking NO-GC in EC. Intriguingly, NO-GC was found to be strongly expressed in retinal pericytes. Our data prove the involvement of NO-GC in growth and plasticity of hindlimb and retinal vasculature after ischemic/hypoxic insult.
一氧化氮（NO）是血管生成和血管新生的重要调节因子，对动脉生成至关重要。NO在体内的作用是否通过对NO敏感的鸟苷酸环化酶（NO-GC）介导，进而通过依赖环磷酸鸟苷（cGMP）的机制介导，目前研究较少。利用两种已建立的动脉生成和血管新生模型，即后肢缺血和氧诱导性视网膜病变，对全身或平滑肌细胞（SMC）或内皮细胞（EC）特异性缺乏NO-GC的小鼠进行研究。我们的数据清楚地表明，NO-GC参与后肢缺血后血流的恢复，这种作用可归因于SMC中的NO-GC。在视网膜中，NO-GC的整体缺失导致氧诱导的血管丢失减少和缺氧诱导的毛细血管再生减少，而病理性新生血管形成增加。在SMC特异性缺失NO-GC的小鼠中也观察到了这些效应，但在EC中缺乏NO-GC的动物中未观察到。有趣的是，发现NO-GC在视网膜周细胞中强烈表达。我们的数据证明，NO-GC参与缺血/缺氧损伤后后肢和视网膜血管系统的生长和可塑性。
