Phosphorylation of Vasodilator-Stimulated Phosphoprotein Prevents Platelet-Neutrophil Complex Formation and Dampens Myocardial Ischemia-Reperfusion Injury
Phosphorylation of Vasodilator-Stimulated Phosphoprotein Prevents Platelet-Neutrophil Complex Formation and Dampens Myocardial Ischemia-Reperfusion Injury
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DOI：
10.1161/circulationaha.110.014555
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发表时间：
2011-06-07
期刊：
影响因子：
37.8
通讯作者：
Rosenberger, Peter
中科院分区：
文献类型：
--
作者：
Koehler, David;Straub, Andreas;Rosenberger, Peter
背景-最近的研究表明，血小板-中性粒细胞复合物（PNC）的形成加重了炎症组织损伤的严重程度。鉴于血管扩张刺激磷蛋白（VASP）的血小板功能的重要性，我们追求的作用VASP的PNC的形成和其对心肌缺血再灌注（IR）injuries.Methods和Results-In的程度的影响，在最初的体外研究中，我们发现，中性粒细胞促进血小板的运动跨内皮细胞单层。VASP的磷酸化减少了PNC的形成和PNC的跨内皮运动。在心肌IR损伤期间，VASP（-/-）动物显示出减少血管内PNC的形成和减少缺血心肌组织内PNC的存在。这与IR损伤减少有关。使用血小板移植和骨髓嵌合体动物的研究表明，造血VASP的表达是至关重要的血管内形成的PNC的存在下，缺血心肌组织内的PNC和心肌IR损伤的程度。此外，VASP在Ser（153）或Ser（235）上的磷酸化减少了血管内PNC的形成和缺血心肌组织内PNC的存在。这一发现与减少心肌IR injure.Conclusion-Previously未得到重视，磷酸化的VASP执行一个关键功能的PNC的形成是至关重要的心肌IR损伤的程度。（循环。2011;123：2579-2590）。
Background-Recent work has suggested that the formation of platelet-neutrophil complexes (PNCs) aggravates the severity of inflammatory tissue injury. Given the importance of vasodilator-stimulated phosphoprotein (VASP) for platelet function, we pursued the role of VASP on the formation of PNCs and its impact on the extent of myocardial ischemia-reperfusion (IR) injury.Methods and Results-In initial in vitro studies we found that neutrophils facilitated the movement of platelets across endothelial monolayers. Phosphorylation of VASP reduced the formation of PNCs and transendothelial movement of PNCs. During myocardial IR injury, VASP(-/-) animals demonstrated reduced intravascular formation of PNCs and reduced presence of PNCs within the ischemic myocardial tissue. This was associated with reduced IR injury. Studies using platelet transfer and bone marrow chimeric animals showed that hematopoietic VASP expression was crucial for the intravascular formation of PNCs the presence of PNCs within ischemic myocardial tissue and the extent of myocardial IR injury. Furthermore, phosphorylation of VASP on Ser(153) or Ser(235) reduced intravascular PNC formation and presence of PNCs within ischemic myocardial tissue. This finding was associated with reduced myocardial IR injury.Conclusion-Previously unappreciated, the phosphorylation of VASP performs a key function for the formation of PNCs that is crucially important for the extent of myocardial IR injury. (Circulation. 2011;123:2579-2590.)