血小板在高血压致心房纤维化以及房颤中的作用机制研究

高血压是导致房颤的危险因素之一，机制尚不明确。血小板的活性在高血压和房颤患者中均显著增高。房颤患者的血小板活化程度与左心房扩张以及心血管死亡事件存在密切的相关性。我们前期结果发现1）高血压合并房颤患者的血小板活性与左心房纤维化呈正相关性；2）蛋白芯片和ELISA结果显示，与健康组相比，高血压合并房颤患者的血小板胞内TGF-β1水平显著降低，而血浆中却显著升高。因此我们假设高血压引起血小板活化，活化的血小板通过释放TGF-β1激活心房成纤维细胞，最终导致心房纤维化和房颤的发生。我们将利用血小板特异性TGF-β1敲除小鼠和抗血小板药物干预小鼠进行血管紧张素2（A2）灌泵，检测心房重构（结构、炎症、纤维化）和电传导，电刺激诱导房颤；建立血小板和原代成纤维细胞共培养体系，探索1）血小板促进A2诱导的心房纤维化的机制；2）血小板选择性活化心房成纤维细胞的机制。该结果将为房颤的治疗和预防提供新思路。

Hypertension is an independent risk factor for atrial fibrillation (AF). However, the mechanisms are still remained unclear. Increasing in platelet activation was associated to LA expansion and cardiac-related death in AF patients, indicating that platelets might contribute to AF. Consistently, our previous results showed that the portion of P-selectin (platelet activation marker) positive platelet was associated with LA fibrosis area in patients with hypertension combined with AF group. Furthermore, protein arrays and ELISA results revealed that levels of transforming growth factor-β1 (TGF-β1) was significantly reduced in platelets from patients with hypertension combined with AF, but significantly increased in plasma. We hypothesize that hypertension induces platelet activation, activated platelet-released TGF-β1 promotes atrial fibroblast activation, eventually contributes to atrial fibrosis and AF. In the present study, we will use platelet conditional knockout mice and anti-platelet drug treated mice to study the role of platelets in atrial fibrosis under the condition of angiotensin II infusion. Moreover, we will set up platelets and atrial/ventricular fibroblasts co-culture condition to explore the mechanism of platelets in promoting atrial fibroblast activation, but not ventricular fibroblasts. Our study will provide promising evidence for using anti-platelet drugs to prevent the development of AF.