Beiert Thomas, Tiyerili Vedat, Knappe Vincent, Effelsberg Verena, Linhart Markus, Stöckigt Florian, Klein Sabine, Schierwagen Robert, Trebicka Jonel, Nickenig Georg, Schrickel Jan W, Andrié René P
Department of Internal Medicine II, University Hospital Bonn, Rheinische Friedrich-Wilhelms University, Bonn, Germany.
Department of Internal Medicine II, University Hospital Bonn, Rheinische Friedrich-Wilhelms University, Bonn, Germany.
Biochem Biophys Res Commun. 2017 Aug 26;490(3):643-649. doi: 10.1016/j.bbrc.2017.06.091. Epub 2017 Jun 17.
Relaxin-2 (RLX) is a peptide hormone that exerts beneficial anti-fibrotic and anti-inflammatory effects in diverse models of cardiovascular disease. The goal of this study was to determine the effects of RLX treatment on the susceptibility to atrial fibrillation (AF) after myocardial infarction (MI).
Mice with cryoinfarction of the left anterior ventricular wall were treated for two weeks with either RLX (75 μg/kg/d) or vehicle (sodium acetate) delivered via subcutaneously implanted osmotic minipumps.
RLX treatment significantly attenuated the increase in AF-inducibility following cryoinfarction and reduced the mean duration of AF episodes. Furthermore, epicardial mapping of both atria revealed an increase in conduction velocity. In addition to an attenuation of atrial hypertrophy, chronic application of RLX reduced atrial fibrosis, which was linked to a significant reduction in atrial mRNA expression of connective tissue growth factor. Transcript levels of the pro-inflammatory cytokines interleukin-6 and interleukin-1β were reduced in RLX treated mice, but macrophage infiltration into atrial myocardium was similar in the vehicle and RLX treated groups.
Treatment with RLX in mice after MI reduces susceptibility to AF due to anti-inflammatory and anti-fibrotic properties. Because to these favorable actions, RLX may become a new therapeutic option in the treatment of AF, even when complicating MI.
松弛素-2（RLX）是一种肽类激素，在多种心血管疾病模型中发挥有益的抗纤维化和抗炎作用。本研究的目的是确定RLX治疗对心肌梗死（MI）后心房颤动（AF）易感性的影响。
通过皮下植入渗透微型泵，用RLX（75μg/kg/d）或赋形剂（醋酸钠）对左前心室壁冷冻梗死的小鼠进行为期两周的治疗。
RLX治疗显著减轻了冷冻梗死后房颤诱导性的增加，并缩短了房颤发作的平均持续时间。此外，对两个心房的心外膜标测显示传导速度增加。除了减轻心房肥大外，长期应用RLX还减少了心房纤维化，这与结缔组织生长因子的心房mRNA表达显著降低有关。在接受RLX治疗的小鼠中，促炎细胞因子白细胞介素-6和白细胞介素-1β的转录水平降低，但在赋形剂组和RLX治疗组中，巨噬细胞浸润到心房心肌中的情况相似。
MI后小鼠接受RLX治疗可降低因抗炎和抗纤维化特性导致的AF易感性。由于这些有利作用，即使在MI并发AF时，RLX也可能成为治疗AF的一种新的治疗选择。
