Changes in aortic reactivity associated with the loss of equilibrative nucleoside transporter 1 (ENT1) in mice.
Changes in aortic reactivity associated with the loss of equilibrative nucleoside transporter 1 (ENT1) in mice.
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DOI：
10.1371/journal.pone.0207198
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Hammond JR
中科院分区：
文献类型：
--
作者：
Best KA;Bone DB;Vilas G;Gros R;Hammond JR
SLc29a1编码平衡核苷转运体亚型1(ENT1)，它是腺苷跨细胞膜转运的主要机制。以往的研究表明，从Slc29a1基因缺失的小鼠分离的组织对血管缺血-再灌注造成的损伤具有相对的抵抗力。为了确定在微血管系统中是否有类似的变化，并研究其潜在的机制，我们研究了野生型和Slc29a1基因缺失的小鼠的主动脉。分别用组织学方法和定量聚合酶链式反应(QPCR)检测主动脉大体结构和基因表达。在常氧和低氧条件下，应用肌丝造影术评价了离体胸主动脉环的收缩特性及其对腺苷的反应。采用尾套法测定体内血流动力学参数。与野生型小鼠相比，SLC29a1基因缺失小鼠的血浆腺苷水平显著升高(2.75倍)，血压显著降低(~15%↓)。来自SLC29a1基因缺失的小鼠的主动脉较硬，周长较小(11%↓)，对氯化钾和受体介导的刺激有增强的收缩反应。用NBS硫代肌苷阻断ENT1可显著增强野生型小鼠的主动脉对苯肾上腺素的反应(约3.5倍)，但对SLc29a1缺失小鼠的主动脉影响甚微。在常氧(11.7倍)和低氧(3.6倍)条件下，腺苷增强了野生型组织中苯肾上腺素介导的收缩，但对SLc29a1缺失的主动脉没有影响。总而言之，来自SLc29a1基因缺失小鼠的动脉对低氧侮辱的反应方式与野生型组织类似，后者已被腺苷药物预适应。这些数据还支持ENT1在腺苷对弹性导管动脉(如胸主动脉)收缩功能的保护作用的调节中的作用。
Slc29a1 encodes for equilibrative nucleoside transporter subtype 1 (ENT1), the primary mechanism of adenosine transfer across cell membranes. Previous studies showed that tissues isolated from Slc29a1-null mice are relatively resistant to injury caused by vascular ischemia-reperfusion. To determine if there are similar changes in the microvasculature, and investigate underlying mechanism, we examined aortas isolated from wildtype and Slc29a1-null mice. Aorta macrostructure and gene expression were examined histologically and by qPCR, respectively. Wire myography was used to assess the contractile properties of isolated thoracic aortic rings and their response to adenosine under both normoxic and hypoxic conditions. In vivo haemodynamic parameters were assessed using the tail-cuff method. Slc29a1-null mice had significantly (P<0.05) increased plasma adenosine (2.75-fold) and lower blood pressure (~15% ↓) than wild-type mice. Aortas from Slc29a1-null mice were stiffer with a smaller circumference (11% ↓), and had an enhanced contractile response to KCl and receptor-mediated stimuli. Blockade of ENT1 with nitrobenzylthioinosine significantly enhanced (by ~3.5-fold) the response of aorta from wild-type mice to phenylephrine, but had minimal effect on aortas from Slc29a1-null mice. Adenosine enhanced phenylephrine-mediated constriction in the wild-type tissue under both normoxic (11.7-fold) and hypoxic (3.6-fold) conditions, but had no effect on the Slc29a1-null aortic aorta. In conclusion, aortas from Slc29a1-null mice respond to hypoxic insult in a manner comparable to wild-type tissues that have been pharmacologically preconditioned with adenosine. These data also support a role for ENT1 in the regulation of the protective effects of adenosine on contractile function in elastic conduit arteries such as thoracic aorta.
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DOI：
10.1080/15257770.2016.1210805
发表时间：
2017-01-02
期刊：
Nucleosides, nucleotides & nucleic acids
影响因子：
--
作者：
Boswell-Casteel RC;Hays FA
通讯作者：
Hays FA
DOI：
10.1152/ajprenal.00581.2012
发表时间：
2013-02-01
影响因子：
4.2
作者：
Li, Lingli;Mizel, Diane;Schnermann, Jurgen
通讯作者：
Schnermann, Jurgen
DOI：
10.1016/j.jchromb.2007.04.013
发表时间：
2007-07-01
影响因子：
3
作者：
Farthing, Don;Sica, Domenic;Karnes, H. Thomas
通讯作者：
Karnes, H. Thomas
影响因子：
20.1
作者：
Casanello, P;Torres, A;Sobrevia, L
通讯作者：
Sobrevia, L
影响因子：
3.1
作者：
Kaneda, Takeharu;Sasaki, Noriyasu;Shimizu, Kazumasa
通讯作者：
Shimizu, Kazumasa