New Strategy for Prevention of Thrombosis by Atrial Fibrillation : From a Viewpoint of Atrial Endocardium

1. 基础研究为了验证卒中心房颤动相关危险因素自身诱导心房心内膜功能障碍的假设，我们测定了老龄大鼠、SHR大鼠和糖尿病大鼠中组织因子通路抑制剂、血栓调节素、eNOS和PAI-1的表达水平。衰老、高血压、糖尿病差异下调心房心内膜TFPI、TM和eNOS，提示危险因素通过心房心内膜功能障碍参与血栓形成。我们还发现肾素-血管紧张素系统在AF心房心内膜功能障碍中发挥重要作用，使用特定的AT1阻滞剂。利用2004-5年Shinken数据库的医院队列，我们确定了RAS抑制剂和他汀类药物对房颤患者卒中发生率的影响。在纳入数据库的4255名患者中，657名患者在初次就诊时患有房颤。RAS抑制剂组和非RAS抑制剂组分别有1.1%和0.9%的患者发生卒中。此外，服用和不服用他汀类药物的患者之间也没有显著差异。需要进一步的研究来确定心内膜靶向策略的效用。

1. Basic ResearchTo test a hypothesis that risk factors for stroke associated with atrial fibrillation (AF) could induce atrial endocardial dysfunction for themselves, we determined the expression level of tissue factor pathway inhibitor, thrombomodulin, eNOS, and PAI-1 in aged rats, SHR, and diabetic rats. Aging, hypertension, diabetes differentially down-regulated TFPI, TM, and eNOS in the atrial endocardium, suggesting that risk factors contribute to thrombus formation via atrial endocardial dysfunction. We also found out that the renin-angiotensin system plays a significant role in the atrial endocardial dysfunction by AF, using a specific AT1 blocker.2. Clinical ResearchUsing our hospital-based cohort of Shinken Database 2004-5, we determined the effects of RAS inhibitors and statins on the incidence of stroke in AF patients. Among the total 4255 patients enrolled into the database, 657 patients had AF at the initial visit. Stroke was observed in 1.1% of patients with RAS inhibitors and in 0.9% of those without, respectively. Also, there were no significant differences between patients with and without statins. Further studies will be required to determine the utility of endocardium-targeted strategy.