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

1.基础研究为了验证房颤（atrial fibrillation，AF）相关的脑卒中危险因素自身可导致心房内膜功能障碍这一假说，我们检测了老年大鼠、自发性高血压大鼠（SHR）和糖尿病大鼠心房组织因子途径抑制物（tissue factor pathway inhibitor，TIMP）、内皮型一氧化氮合酶（eNOS）和纤溶酶原激活物抑制物-1（派-1）的表达水平。老年、高血压、糖尿病差异性下调心房内膜TFPI、TM和eNOS，提示心房内膜功能障碍是血栓形成的危险因素。我们还发现，使用特定的AT 1阻断剂，肾素-血管紧张素系统在AF引起的心房内膜功能障碍中起重要作用.临床研究使用我们的医院队列的Shinken数据库2004-5，我们确定了RAS抑制剂和他汀类药物对AF患者卒中发生率的影响。在入组数据库的4255例患者中，657例患者在首次访视时患有AF。分别在1.1%的RAS抑制剂患者和0.9%的无RAS抑制剂患者中观察到卒中。此外，有和没有他汀类药物的患者之间没有显着差异。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.