Enhancement of Endothelial Function Inhibits Left Atrial Thrombi Development in an Animal Model of Spontaneous Left Atrial Thrombosis
Enhancement of Endothelial Function Inhibits Left Atrial Thrombi Development in an Animal Model of Spontaneous Left Atrial Thrombosis
复制标题
DOI：
10.1253/circj.cj-13-1398
复制
发表时间：
2014-08-01
影响因子：
3.3
通讯作者：
Nakaya, Yutaka
中科院分区：
文献类型：
--
作者：
Mawatari, Kazuaki;Yoshioka, Emiko;Nakaya, Yutaka
背景：左房血栓形成是全身栓塞的重要原因。先前建立了具有高自愿性车轮跑特点的LA血栓(自发跑)运动大鼠模型。方法和结果：心血管内皮细胞产生的一氧化氮(NO)在局部血流调节、血管张力和血小板聚集中起重要的保护作用。无论年龄大小，运动大鼠均未发现心房颤动或高凝状态的证据；然而，运动大鼠从小就表现出内皮功能障碍和NO产生的减少。此外，运动组大鼠左房和胸主动脉内皮细胞内皮细胞一氧化氮合酶活性显著降低。虽然自愿的车轮运动能够间歇性地增加NO水平，但在尸检时，跑步并不能从统计学上降低LA血栓的发生率。结论：本研究结果表明，NO在运动大鼠LA血栓形成过程中起重要作用，血管内皮细胞通路可为预防LA血栓形成提供新的治疗靶点。
Background: Left atrial (LA) thrombosis is an important cause of systemic embolization. The SPORTS rat model of LA thrombi (Spontaneously-Running Tokushima-Shikoku), which have a unique characteristic of high voluntary wheel running, was previously established. The aim of the present study was to investigate how SPORTS rats develop LA thrombi.Methods and Results: Nitric oxide (NO) produced from cardiovascular endothelial cells plays an important protective role in the local regulation of blood flow, vascular tone, and platelet aggregation. No evidence of atrial fibrillation or hypercoagulability in SPORTS rats regardless of age was found; however, SPORTS rats demonstrated endothelial dysfunction and a decrease of NO production from a young age. In addition, endothelial NO synthase activity was significantly decreased in the LA and thoracic aorta endothelia of SPORTS rats. While voluntary wheel running was able to intermittently increase NO levels, running did not statistically decrease the incidence of LA thrombi at autopsy. However, L-arginine treatment significantly increased NO production and provided protection from the development of LA thrombi in SPORTS rats.Conclusions: They present study results indicate that NO has an important role in the development of LA thrombus, and endothelia pathways could provide new targets of therapy to prevent LA thrombosis.