MicroRNA-146a Regulates Perfusion Recovery in Response to Arterial Occlusion via Arteriogenesis.
MicroRNA-146a Regulates Perfusion Recovery in Response to Arterial Occlusion via Arteriogenesis.
复制标题
MicroRNA-146A通过动脉生成来调节灌注恢复，以应对动脉闭塞。
DOI：
10.3389/fbioe.2018.00001
复制
发表时间：
2018
影响因子：
5.7
通讯作者：
Price RJ
中科院分区：
文献类型：
--
作者：
Heuslein JL;McDonnell SP;Song J;Annex BH;Price RJ
绕过动脉闭塞的内源性侧支动脉的生长或动脉生成是基本的剪切应力诱导的适应，其对于治疗外周动脉疾病具有意义。微小RNA（miRs）是响应损伤的基因表达的关键调节因子，并且具有强大的治疗潜力。在先前的研究中，我们将miR-146 a确定为血管重塑的候选调节因子。在这里，我们测试了miR-146 a是否调节体外血管生成内皮细胞（EC）的行为，以及体内股动脉结扎（FAL）后的灌注恢复、动脉生成和血管生成。我们发现miR-146 a抑制在体外损害EC管形成和迁移。在FAL后，Balb/c小鼠用抗miR-146 a或乱序锁核酸（LNA）寡核苷酸直接单次肌内注射到非缺血性股薄肌中进行处理。连续激光多普勒成像显示，与用乱序LNA处理的小鼠相比，抗miR-146 a处理的小鼠表现出显著更大的灌注恢复（增加16%）。此外，与对照组相比，抗miR-146 a处理的小鼠显示侧支动脉直径增加22%，而对体内血管生成或肌肉再生没有显著影响。尽管对血管生成没有发挥有益作用，但机械敏感性miR-146 a的抑制通过增强动脉生成增强了FAL后的灌注恢复。
The growth of endogenous collateral arteries that bypass arterial occlusion(s), or arteriogenesis, is a fundamental shear stress-induced adaptation with implications for treating peripheral arterial disease. MicroRNAs (miRs) are key regulators of gene expression in response to injury and have strong therapeutic potential. In a previous study, we identified miR-146a as a candidate regulator of vascular remodeling. Here, we tested whether miR-146a regulates in vitro angiogenic endothelial cell (EC) behaviors, as well as perfusion recovery, arteriogenesis, and angiogenesis in response to femoral arterial ligation (FAL) in vivo. We found miR-146a inhibition impaired EC tube formation and migration in vitro. Following FAL, Balb/c mice were treated with a single, intramuscular injection of anti-miR-146a or scramble locked nucleic acid (LNA) oligonucleotides directly into the non-ischemic gracilis muscles. Serial laser Doppler imaging demonstrated that anti-miR-146a treated mice exhibited significantly greater perfusion recovery (a 16% increase) compared mice treated with scramble LNA. Moreover, anti-miR-146a treated mice exhibited a 22% increase in collateral artery diameter compared to controls, while there was no significant effect on in vivo angiogenesis or muscle regeneration. Despite exerting no beneficial effects on angiogenesis, the inhibition of mechanosensitive miR-146a enhances perfusion recovery after FAL via enhanced arteriogenesis.
登录
查看更多内容
DOI：
10.1161/atvbaha.111.230441
发表时间：
2011-11
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Duscha BD;Robbins JL;Jones WS;Kraus WE;Lye RJ;Sanders JM;Allen JD;Regensteiner JG;Hiatt WR;Annex BH
通讯作者：
Annex BH
DOI：
10.1152/ajpheart.00772.2008
发表时间：
2009-03-01
影响因子：
4.8
作者：
Distasi, Matthew R.;Case, Jamie;Unthank, Joseph L.
通讯作者：
Unthank, Joseph L.
影响因子：
11.1
作者：
Cheng, Henry S.;Sivachandran, Nirojini;Lau, Andrew;Boudreau, Emilie;Zhao, Jimmy L.;Baltimore, David;Delgado-Olguin, Paul;Cybulsky, Myron I.;Fish, Jason E.
通讯作者：
Fish, Jason E.
DOI：
10.1006/bbrc.1994.1794
发表时间：
1994-06-15
影响因子：
3.1
作者：
LAN, QX;MERCURIUS, KO;DAVIES, PF
通讯作者：
DAVIES, PF
影响因子：
37.8
作者：
Grundmann, Sebastian;Hans, Felix P.;Moser, Martin
通讯作者：
Moser, Martin