BF061, a novel antiplatelet and antithrombotic agent targeting P2Y(12) receptor and phosphodiesterase
文献类型：期刊论文
| 作者 | Hu, L; Fan, ZC; Du, HG; Ni, R; Zhang, S; Yin, KH; Ye, JQ; Zhang, Y; Wei, XB; Zhang, XH |
| 刊名 | THROMBOSIS AND HAEMOSTASIS
 |
| 出版日期 | 2011 |
| 卷号 | 106期号:6页码:1203-1214 |
| 关键词 | Antiplatelet antithrombotic BF061 PDE inhibitor P2Y(12) receptor antagonist |
| 通讯作者 | Ding, ZR (reprint author), Fudan Univ, Shanghai Med Coll, Key Lab Mol Med, Minist Educ, Shanghai 200032, Peoples R China.,dingzr@fudan.edu.cn |
| 英文摘要 | The addition of phosphodiesterase (PDE) inhibitors has been reported to potentiate the antithrombotic effects of P2Y(12) antagonists without increasing bleeding risk. In this study, we report that a potent antiplatelet agent, 2-ethylthio-6-phenethylaminoadenosine (BF061), inhibits platelet activation and thrombosis via P2Y(12) antagonism and PDE inhibition. We explored the antiplatelet mechanism of BF061 by measuring cAMP, cGMP levels, PDE activity, and the interaction between ADP and P2Y(12) using atomic force microscopy. The antithrombotic effect of BF061 was evaluated in mice using intravital microscopy in FeCl(3)-induced mesenteric and laser-induced cremasteric arterial thrombosis models. BF061 robustly inhibited platelet aggregation and ATP release induced by multiple platelet agonists via P2Y(12) antagonism and PDE inhibition. Interestingly, despite being structurally similar to BF061, P2Y(12) receptor antagonist AR-C69931MX had no effect on human platelet PDE. In FeCl(3)-induced mesenteric arterial thrombosis model, BF061 effectively prevented thrombus formation similarly to clopidogrel; it also reduced thrombus volume in laser-injured cremaster arteriole model. In contrast, BF061 induced dramatically less bleeding at an antithrombotic dose compared to clopidogrel. In summary, we developed a novel antiplatelet and antithrombotic agent targeting both P2Y(12) and PDE. Given the prevalence of combined antiplatelet therapy in clinical practice, an antiplatelet agent bearing dual activities may have therapeutic advantage as a potential antithrombotic drug. |
| 学科主题 | Hematology; Cardiovascular System & Cardiology |
| 类目[WOS] | Hematology ; Peripheral Vascular Disease |
| 关键词[WOS] | ELUTING STENT IMPLANTATION ; PERCUTANEOUS CORONARY INTERVENTION ; PLATELET-AGGREGATION ; IN-VIVO ; THERAPY ; CILOSTAZOL ; TRIPLE ; THROMBOSIS ; MICE ; COMPLICATIONS |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000298719100025 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/817]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Hu, L,Fan, ZC,Du, HG,et al. BF061, a novel antiplatelet and antithrombotic agent targeting P2Y(12) receptor and phosphodiesterase[J]. THROMBOSIS AND HAEMOSTASIS,2011,106(6):1203-1214. |
| APA | Hu, L.,Fan, ZC.,Du, HG.,Ni, R.,Zhang, S.,...&Ding, ZR.(2011).BF061, a novel antiplatelet and antithrombotic agent targeting P2Y(12) receptor and phosphodiesterase.THROMBOSIS AND HAEMOSTASIS,106(6),1203-1214. |
| MLA | Hu, L,et al."BF061, a novel antiplatelet and antithrombotic agent targeting P2Y(12) receptor and phosphodiesterase".THROMBOSIS AND HAEMOSTASIS 106.6(2011):1203-1214. |
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