The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Shandong University, No 107 Wenhua West Road, Ji'nan, 250012, China.
Department of Cardiology, Yantai Yuhuangding Hospital, Qingdao Medical College, Qingdao University, Yantai, China.
BMC Cardiovasc Disord. 2020 Feb 14;20(1):81. doi: 10.1186/s12872-019-01289-z.
Tanshinone IIA (TS IIA), a multi-pharmaceutical compound from traditional Chinese herb, is effective for treatment of atherothrombosis. However, the underlying mechanisms of TS IIA-mediated anti-platelet activation effect are still poorly understood. As shown in our previous study, platelet-derived microvesicles (PMVs) generated in response to oxidant insult could activate CD36/mitogen-activated protein kinase kinase 4/Jun N-terminal kinase 2 (CD36/MKK4/JNK2) signals and lead to platelet activation. The present study aims to investigate the effect of TS IIA on platelet activation and the possible mechanisms.
The production of PMVs induced by Interleukin 6 (IL-6) was detected by flow cytometry. We performed activating studies of platelets with PMVs derived from IL-6-treated platelets (IL-6-PMVs) in vitro. Sometimes, platelet suspensions were incubated with serial concentrations of TS IIA for 15 min before being stimulated with IL-6-PMVs. Expression of platelet integrin αβ and CD36 was detected by flow cytometry. Phosphorylation of MKK4 and JNK were detected by immunoblotting.
Here we demonstrated firstly that TS IIA could prevent platelet activation induced by PMVs and down-regulates CD36 and MKK4/JNK2 signaling pathway. CD36 may be the target of atherosclerosis (AS)-related thrombosis.
This study showed the possible mechanisms of TS IIA-mediated anti-platelet activation and may provide a new strategy for the treatment of AS-related thrombosis by targeting platelet CD36.
丹参酮 IIA（TS IIA）是一种来自传统中药的多药物化合物，对动脉血栓形成治疗有效。然而，TS IIA 介导的抗血小板活化作用的潜在机制仍知之甚少。正如我们之前的研究所示，氧化应激诱导产生的血小板衍生微小囊泡（PMVs）可以激活 CD36/丝裂原活化蛋白激酶激酶 4/Jun N-末端激酶 2（CD36/MKK4/JNK2）信号，导致血小板活化。本研究旨在探讨 TS IIA 对血小板活化的影响及其可能的机制。
通过流式细胞术检测白细胞介素 6（IL-6）诱导的 PMVs 的产生。我们在体外使用 IL-6 处理的血小板衍生的微小囊泡（IL-6-PMVs）对血小板进行激活研究。有时，在刺激 IL-6-PMVs 之前，将血小板悬浮液与系列浓度的 TS IIA 孵育 15 分钟。通过流式细胞术检测血小板整合素 αβ和 CD36 的表达。通过免疫印迹检测 MKK4 和 JNK 的磷酸化。
我们首次证明 TS IIA 可以防止 PMVs 诱导的血小板活化，并下调 CD36 和 MKK4/JNK2 信号通路。CD36 可能是动脉粥样硬化（AS）相关血栓形成的靶点。
本研究显示了 TS IIA 介导的抗血小板活化的可能机制，并可能通过靶向血小板 CD36 为 AS 相关血栓形成的治疗提供新策略。
