Centro Cardiologico Monzino, I.R.C.C.S, Milan, Italy.
Exp Hematol. 2010 May;38(5):341-50. doi: 10.1016/j.exphem.2010.03.001. Epub 2010 Mar 11.
This study aimed at investigating the protein patterns of platelets from patients with stable or acute coronary atherosclerosis (CAD), in which platelets play a key role.
A proteomic approach was adopted to investigate specific protein patterns in platelets of patients with non-ST elevation acute coronary syndrome, stable angina, or of subjects with no history of CAD.
Six differentially expressed proteins were identified: two involved in energy metabolism (2-oxoglutarate dehydrogenase [OGDH], and lactate dehydrogenase [LDH]); three were associated with cytoskeleton-based processes (gamma-actin, coronin 1B, and pleckstrin); and one involved in protein degradation (proteasome subunit type 8). Expression levels of OGDH and a cleaved form of gamma-actin were significantly higher in the platelets of patients than in controls, whereas that of LDH was higher only in the platelets of patients with acute coronary disease. The increases in protein expression of OGDH and LDH are paralleled by changes in their functional activities. Coronin and proteasome subunit type 8 were less expressed in the platelets of patients, as were the basic isoforms of pleckstrin.
The platelet proteome is altered in CAD patients with stable or acute coronary syndrome possibly because of the ongoing atherosclerotic process. The identified protein changes not previously connected with CAD were an increase in the energy metabolism enzymes and alterations in the proteins associated with cytoskeleton-based processes, both of which indicate platelet activation.
本研究旨在探讨稳定或急性冠状动脉粥样硬化(CAD)患者血小板中的蛋白质图谱,因为血小板在其中发挥着关键作用。
采用蛋白质组学方法研究非 ST 段抬高急性冠状动脉综合征、稳定型心绞痛患者或无 CAD 病史患者的血小板中特定的蛋白质图谱。
鉴定出 6 种差异表达的蛋白质:两种与能量代谢有关(2-氧戊二酸脱氢酶[OGDH]和乳酸脱氢酶[LDH]);三种与细胞骨架相关的过程有关(γ-肌动蛋白、冠蛋白 1B 和衔接蛋白);一种与蛋白质降解有关(蛋白酶体亚基 8)。与对照组相比,急性冠脉疾病患者的血小板中 OGDH 和 γ-肌动蛋白的切割形式的表达水平明显升高,而 LDH 仅在急性冠脉疾病患者的血小板中升高。OGDH 和 LDH 蛋白表达的增加与它们的功能活性的变化相平行。冠蛋白和蛋白酶体亚基 8 在患者的血小板中表达减少,衔接蛋白的基础同工型也是如此。
稳定或急性冠状动脉综合征的 CAD 患者的血小板蛋白质组发生改变,可能是由于持续的动脉粥样硬化过程。与 CAD 以前没有联系的鉴定出的蛋白质变化是能量代谢酶的增加和与细胞骨架相关的过程的蛋白质的改变,这两者都表明血小板的激活。