Letter by Papangeli et al Regarding Article, "The ERG-APLNR Axis Controls Pulmonary Venule Endothelial Proliferation in Pulmonary Veno-Occlusive Disease".
Letter by Papangeli et al Regarding Article, "The ERG-APLNR Axis Controls Pulmonary Venule Endothelial Proliferation in Pulmonary Veno-Occlusive Disease".
复制标题
Papangeli 等人关于文章“ERG-APLNR 轴控制肺静脉闭塞性疾病中的肺小静脉内皮增殖”的信函。
DOI：
10.1161/circulationaha.114.012494
复制
发表时间：
2015
期刊：
影响因子：
37.8
通讯作者：
Chun,HyungJ
中科院分区：
文献类型：
--
作者：
Papangeli,Irinna;Sharma,Bikram;Chun,HyungJ
我们怀着极大的兴趣阅读了Lathen及其同事题为“The ERG-APLNR Axis Controls Pulmonary Venule Endothelial Proliferation in Pulmonary Veno-Occlusive Disease”的文章，并祝贺作者使用人类样本和现代遗传技术的全面方法。1然而，我们认为有两个关键点值得注意。首先，在文献综述之后，作者得出结论：“这些研究指出了Aplnr信号传导对静脉循环具有直接和独特影响的概念。然而，大多数引用的研究没有描述静脉特异性机制。Cheng等人2证明，apelin给药降低了大鼠的平均动脉压和平均循环充盈压，总结称“apelin是体内动脉和静脉扩张剂”。考克斯和同事3在青蛙胚胎上使用了珠粒趋化模型;尽管apelin浸泡的珠粒诱导了主静脉区域的发芽，但对apelin的反应与血管内皮生长因子浸泡的珠粒相当，并且不排除对apelin有反应的非静脉内皮细胞。最后，作者引用了Eyries及其同事4的工作，该工作使用斑马鱼尾鳍截肢模型来研究apelin对再生血管生成的贡献。该模型不是静脉再生的特异性模型，也不是本文中讨论的爱帕琳肽对血管再生的静脉特异性血管生成作用。4更重要的是，我们已经评估了成年小鼠肺中Aplnr的表达，使用Microfil注射到右心室中以有效地描绘肺动脉树。我们通过使用两种独立的方法发现肺小动脉内皮中Aplnr的稳健表达：（1）原位杂交（由于缺乏稳健的Aplnr抗体）和（2）来自最近开发的AplnrCreER：RosamTmG小鼠的绿色荧光蛋白表达。5 Lathen及其同事报道，较大的肺动脉不表达Aplnr。虽然我们不能完全排除可能介导apelin在肺动脉高压中的作用的次级但未鉴定的apelin受体的可能性，但我们的研究结果提供了强有力的证据，即Aplnr，鉴于其在肺小动脉中的稳健表达，肯定可以是介导apelin在肺动脉高压中的作用的关键受体。第二，在肺静脉内皮细胞中响应于腺病毒Erg表达的Aplnr的选择性诱导，而不是任何其他经验证的Erg转录靶，以及Erg和Aplnr在体内表达的不同模式，强调了在理解Erg活性如何调节和选择性地诱导动脉和静脉内皮细胞中的一些转录靶点而不是其他靶点方面的局限性。Lathen和同事1对肺静脉闭塞性疾病的新机制提供了有趣的见解;然而，我们认为Aplnr在肺血管系统中的作用超出了肺静脉系统，并希望确保Aplnr的肺小动脉表达不被低估。
We have read with great interest the article by Lathen and colleagues titled “The ERG–APLNR Axis Controls Pulmonary Venule Endothelial Proliferation in Pulmonary Veno-Occlusive Disease,” and congratulate the authors for their thorough approach using human samples and modern genetic techniques. 1 However, there are 2 key points that, in our opinion, deserve attention. First, following a literature review, the authors conclude that “These studies point to the concept that Aplnr signaling has direct and unique effects on the venous circulation.” However, the majority of the cited studies do not describe venous-specific mechanisms. Cheng et al2 demonstrated that apelin administration decreased both the mean arterial pressure and the mean circulatory filling pressure in rats, summarizing that “apelin is an arterial and venous dilator in vivo.” Cox and colleagues3 used a bead chemotaxis model on frog embryos; although apelin-soaked beads induced sprouting from the cardinal vein region, the response to apelin was comparable to vascular endothelial growth factor–soaked beads and did not exclude nonvenous endothelial cells responding to apelin. Last, the authors invoke work by Eyries and colleagues4 that used the zebrafish caudal fin amputation model to study the apelin contribution on regenerative angiogenesis. This model is not specific to venous regeneration, nor is a venous-specific angiogenic effect of apelin toward vascular regeneration discussed in this article. 4 More importantly, we have evaluated Aplnr expression in the adult mouse lung, using Microfil injected into the right ventricle to effectively delineate the pulmonary arterial tree. We found robust expression of Aplnr in the pulmonary arteriolar endothelium by using 2 independent approaches:(1) in situ hybridization (given the paucity of a robust Aplnr antibody) and (2) green fluorescent protein expression from the recently developed AplnrCreER: RosamTmG mice. 5 The larger pulmonary arteries did not express Aplnr, as reported by Lathen and colleagues. Although we cannot fully exclude the possibility of a secondary, yet unidentified apelin receptor that may be mediating the effects of apelin in pulmonary arterial hypertension, our findings provide strong evidence that Aplnr, given its robust expression in the pulmonary arterioles, can certainly be the key receptor that mediates the effects of apelin in pulmonary arterial hypertension. Second, the selective induction of Aplnr in response to adenoviral Erg expression in the pulmonary venous endothelial cells, but not any of the other validated Erg transcriptional targets, and the disparate pattern of Erg and Aplnr expression in vivo, highlight the limitations in understanding how Erg activity is regulated and selectively induce some transcriptional targets but not others in the arterial and venous endothelial cells.The referenced work by Lathen and colleagues1 provides interesting insights into a novel mechanism of pulmonary veno-occlusive disease; nevertheless, we believe that the roles of Aplnr in the pulmonary vasculature extend beyond the pulmonary venous system, and would like to ensure that the pulmonary arteriole expression of Aplnr is not understated.
致命军团病与免疫抑制治疗的开始同时发生。
影响因子：
--
作者：
P. Sheldon;R. Tight;E. Renner
通讯作者：
E. Renner