Department of Pharmacology, Faculty of Pharmacy and Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
Arterioscler Thromb Vasc Biol. 2011 Dec;31(12):2957-64. doi: 10.1161/ATVBAHA.111.235713. Epub 2011 Sep 15.
Our aim in this study was to provide novel information on the molecular mechanisms playing a major role in the unwanted platelet activation associated with ST-elevation myocardial infarction (STEMI).
We compared the platelet proteome of 11 STEMI patients to a matched control group of 15 stable chronic ischemic cardiopathy patients. In addition, we did a prospective study to follow the STEMI patients over time. Proteins were separated by high-resolution 2D gel electrophoresis, identified by mass spectrometry, and validated by Western blotting. Platelets from STEMI patients on admission displayed 56 protein spot differences (corresponding to 42 unique genes) compared with the control group. The number of differences decreased with time during the patients' follow-up. Interestingly, the adapter protein CrkL and the active form of Src (phosphorylated in Tyr418) were found to be upregulated in platelets from STEMI patients. Major signaling pathways related to the proteins identified include integrin, integrin-linked kinase, and glycoprotein VI (GPVI) signaling. Interestingly, a study on an independent cohort of patients showed a higher degree of activation of GPVI signaling in STEMI patients.
CrkL, the active form of Src, and GPVI signaling are upregulated in platelets from STEMI patients.
本研究旨在提供与 ST 段抬高型心肌梗死（STEMI）相关的血小板非预期激活的主要分子机制的新信息。
我们比较了 11 例 STEMI 患者与 15 例稳定型慢性缺血性心脏病患者的血小板蛋白质组。此外，我们进行了一项前瞻性研究，以随时间观察 STEMI 患者。使用高分辨率 2D 凝胶电泳分离蛋白质，通过质谱鉴定，并通过 Western blot 验证。与对照组相比，入院时 STEMI 患者的血小板显示出 56 个蛋白斑点差异（对应于 42 个独特基因）。在患者随访期间，差异数量随时间减少。有趣的是，衔接蛋白 CrkL 和Src 的活性形式（Tyr418 磷酸化）被发现在上皮细胞中上调。与鉴定的蛋白质相关的主要信号通路包括整合素、整合素连接激酶和糖蛋白 VI（GPVI）信号通路。有趣的是，对另一组患者的研究表明，STEMI 患者的 GPVI 信号通路激活程度更高。
CrkL、Src 的活性形式和 GPVI 信号通路在上皮细胞中上调。
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