Eberini Ivano, Gianazza Elisabetta, Breghi Loranni, Klugmann Silvio, Calabresi Laura, Gomaraschi Monica, Mombelli Giuliana, Brusoni Bruno, Wait Robin, Sirtori Cesare R
Proteomics and Protein Structure Study Group, University of Milan, Milan, Italy.
Ann Med. 2007;39(4):306-11. doi: 10.1080/07853890701288760.
The outcome of percutaneous coronary intervention (PCI) is apparently worse in patients receiving a prior thrombolytic therapy ('facilitated PCI'). Recombinant tissue-type plasminogen activator (rt-PA) can degrade circulating high-density lipoproteins (HDL) bound apolipoprotein A-I (apoA-I), thus possibly reducing the vascular protective activity. There have never been reports of the detection of apolipoprotein breakdown products in the circulation.
We studied the potential interactions between the protein components of HDL and tenecteplase, infused as thrombolytic therapy.
Sera from a total of 40 patients with acute myocardial infarction (AMI), unstable angina (UA), and dilative cardiomyopathy (controls) were investigated. AMI patients underwent either immediate PCI or were treated with tenecteplase thrombolysis.
Products of extensive proteolysis of apoA-I were found in many acute coronary patients treated with tenecteplase, and in some AMI patients before starting the treatment (time 0). These were not detected in controls, UA patients as well as AMI patients undergoing immediate PCI. Small pre-beta-HDLs were selectively degraded.
Significant apoA-I degradation occurs in AMI patients after thrombolytic treatment. This finding may provide a potential mechanism for the apparent reduction of benefit of facilitated versus nonfacilitated PCI.
接受过先前溶栓治疗（“易化PCI”）的患者经皮冠状动脉介入治疗（PCI）的结果明显更差。重组组织型纤溶酶原激活剂（rt-PA）可降解与循环高密度脂蛋白（HDL）结合的载脂蛋白A-I（apoA-I），从而可能降低血管保护活性。此前从未有关于在循环中检测到载脂蛋白降解产物的报道。
我们研究了作为溶栓治疗药物注入的替奈普酶与HDL蛋白质成分之间的潜在相互作用。
共对40例急性心肌梗死（AMI）、不稳定型心绞痛（UA）患者以及扩张型心肌病患者（对照组）的血清进行了研究。AMI患者接受了直接PCI或替奈普酶溶栓治疗。
在许多接受替奈普酶治疗的急性冠脉疾病患者以及部分AMI患者治疗开始前（时间0）发现了apoA-I广泛蛋白水解的产物。在对照组患者、UA患者以及接受直接PCI的AMI患者中未检测到这些产物。前β-HDL小颗粒被选择性降解。
溶栓治疗后AMI患者发生了显著的apoA-I降解。这一发现可能为易化PCI与非易化PCI相比获益明显降低提供了一种潜在机制。
