Gao Xiao-Ming, Moore Xiao-Lei, Liu Yang, Wang Xin-Yu, Han Li-Ping, Su Yidan, Tsai Alan, Xu Qi, Zhang Ming, Lambert Gavin W, Kiriazis Helen, Gao Wei, Dart Anthony M, Du Xiao-Jun
Experimental Cardiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, VIC 3004, Australia Central Clinical School, Monash University, Melbourne, VIC 3004, Australia.
Experimental Cardiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, VIC 3004, Australia Alfred Heart Centre, Alfred Hospital, Melbourne, VIC 3004, Australia.
Clin Sci (Lond). 2016 Jul 1;130(13):1089-104. doi: 10.1042/CS20160234. Epub 2016 Apr 5.
Acute myocardial infarction (AMI) is characterized by a rapid increase in circulating platelet size but the mechanism for this is unclear. Large platelets are hyperactive and associated with adverse clinical outcomes. We determined mean platelet volume (MPV) and platelet-monocyte conjugation (PMC) using blood samples from patients, and blood and the spleen from mice with AMI. We further measured changes in platelet size, PMC, cardiac and splenic contents of platelets and leucocyte infiltration into the mouse heart. In AMI patients, circulating MPV and PMC increased at 1-3 h post-MI and MPV returned to reference levels within 24 h after admission. In mice with MI, increases in platelet size and PMC became evident within 12 h and were sustained up to 72 h. Splenic platelets are bigger than circulating platelets in normal or infarct mice. At 24 h post-MI, splenic platelet storage was halved whereas cardiac platelets increased by 4-fold. Splenectomy attenuated all changes observed in the blood, reduced leucocyte and platelet accumulation in the infarct myocardium, limited infarct size and alleviated cardiac dilatation and dysfunction. AMI-induced elevated circulating levels of adenosine diphosphate and catecholamines in both human and the mouse, which may trigger splenic platelet release. Pharmacological inhibition of angiotensin-converting enzyme, β1-adrenergic receptor or platelet P2Y12 receptor reduced platelet abundance in the murine infarct myocardium albeit having diverse effects on platelet size and PMC. In conclusion, AMI evokes release of splenic platelets, which contributes to the increase in platelet size and PMC and facilitates myocardial accumulation of platelets and leucocytes, thereby promoting post-infarct inflammation.
急性心肌梗死（AMI）的特征是循环血小板大小迅速增加，但其机制尚不清楚。大血小板活性过高，并与不良临床结局相关。我们使用患者的血液样本以及急性心肌梗死小鼠的血液和脾脏，测定了平均血小板体积（MPV）和血小板 - 单核细胞结合（PMC）。我们进一步测量了血小板大小、PMC、心脏和脾脏中血小板含量的变化以及白细胞向小鼠心脏的浸润情况。在急性心肌梗死患者中，循环中的MPV和PMC在心肌梗死后1 - 3小时增加，入院后24小时内MPV恢复至参考水平。在心肌梗死小鼠中，血小板大小和PMC在12小时内明显增加，并持续至72小时。在正常或梗死小鼠中，脾脏血小板比循环血小板大。心肌梗死后24小时，脾脏血小板储存量减半，而心脏血小板增加了4倍。脾切除术减弱了血液中观察到的所有变化，减少了梗死心肌中的白细胞和血小板积聚，限制了梗死面积，并减轻了心脏扩张和功能障碍。急性心肌梗死导致人和小鼠体内循环中的二磷酸腺苷和儿茶酚胺水平升高，这可能触发脾脏血小板释放。血管紧张素转换酶、β1 - 肾上腺素能受体或血小板P2Y12受体的药理学抑制作用降低了小鼠梗死心肌中的血小板丰度，尽管对血小板大小和PMC有不同影响。总之，急性心肌梗死引发脾脏血小板释放，这有助于血小板大小和PMC增加，并促进血小板和白细胞在心肌中的积聚，从而促进梗死后炎症反应。
