Cell-specific impact of nitric oxide-dependent guanylyl cyclase on arteriogenesis and angiogenesis in mice
Cell-specific impact of nitric oxide-dependent guanylyl cyclase on arteriogenesis and angiogenesis in mice
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DOI：
10.1007/s10456-015-9463-8
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发表时间：
2015-07-01
期刊：
影响因子：
9.8
通讯作者：
Friebe, Andreas
中科院分区：
文献类型：
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作者：
Bettaga, Noomen;Jaeger, Ronald;Friebe, Andreas
一氧化氮 (NO) 是血管生成和血管生成的重要调节剂，对动脉生成至关重要。 NO 在体内的作用是否是通过 NO 敏感鸟苷酸环化酶 (NO-GC) 介导的，从而是通过 cGMP 依赖性机制介导的，目前还不清楚。对整体或平滑肌细胞 (SMC) 或内皮细胞 (EC) 中缺乏 NO-GC 的小鼠进行两种已建立的动脉生成和血管生成模型，即后肢缺血和氧诱导的视网膜病变。我们的数据清楚地表明NO-GC参与后肢缺血后血流的恢复，这种作用可能归因于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损失和缺氧诱导的毛细血管再生减少，而病理性新血管形成增加。这些效应在 SMC 特异性 NO-GC 缺失的小鼠中也可见到，但在 EC 中缺乏 NO-GC 的动物中却没有。有趣的是，NO-GC被发现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脉管系统的生长和可塑性。
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.