Lang Alexander, Oehler Daniel, Benkhoff Marcel, Reinders Yvonne, Barcik Maike, Shahrjerdi Khatereh, Kaldirim Madlen, Sickmann Albert, Dannenberg Lisa, Polzin Amin, Pfeiler Susanne, Kelm Malte, Grandoch Maria, Jung Christian, Gerdes Norbert
Division of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty and University Hospital, Heinrich-Heine University, 40225 Düsseldorf, Germany.
Leibniz-Institut für Analytische Wissenschaften-ISAS-e.V., 44139 Dortmund, Germany.
Biomedicines. 2024 Oct 16;12(10):2368. doi: 10.3390/biomedicines12102368.
BACKGROUND/OBJECTIVES: Acute myocardial infarction (AMI), characterized by irreversible heart muscle damage and impaired cardiac function caused by myocardial ischemia, is a leading cause of global mortality. The damage associated with reperfusion, particularly mitochondrial dysfunction and reactive oxygen species (ROS) formation, has emerged as a crucial factor in the pathogenesis of cardiac diseases, leading to the recognition of mitochondrial proteins as potential markers for myocardial damage. This study aimed to identify differentially expressed proteins based on the type of cardiac injury, in particular those with and without reperfusion.
Male C57Bl/6J mice were either left untreated, sham-operated, received non-reperfused AMI, or reperfused AMI. Twenty-four hours after the procedures, left ventricular (LV) function and morphological changes including infarct size were determined using echocardiography and triphenyl tetrazolium chloride (TTC) staining, respectively. In addition, plasma was isolated and subjected to untargeted mass spectrometry and, further on, the ELISA-based validation of candidate proteins.
We identified mitochondrial creatine kinase 2 (Ckmt2) as a differentially regulated protein in plasma of mice with reperfused but not non-reperfused AMI. Elevated levels of Ckmt2 were significantly associated with infarct size and impaired LV function following reperfused AMI, suggesting a specific involvement in reperfusion damage.
Our study highlights the potential of plasma Ckmt2 as a biomarker for assessing reperfusion injury and its impact on cardiac function and morphology in the acute phase of MI.
背景/目的：急性心肌梗死（AMI）以心肌缺血导致的不可逆心肌损伤和心功能受损为特征，是全球死亡的主要原因。与再灌注相关的损伤，特别是线粒体功能障碍和活性氧（ROS）形成，已成为心脏疾病发病机制中的关键因素，这使得线粒体蛋白被认为是心肌损伤的潜在标志物。本研究旨在根据心脏损伤类型，特别是有无再灌注的情况，鉴定差异表达的蛋白质。
雄性C57Bl/6J小鼠分为未处理组、假手术组、非再灌注AMI组或再灌注AMI组。手术后24小时，分别使用超声心动图和氯化三苯基四氮唑（TTC）染色测定左心室（LV）功能和包括梗死面积在内的形态学变化。此外，分离血浆并进行非靶向质谱分析，进一步基于酶联免疫吸附测定（ELISA）对候选蛋白进行验证。
我们鉴定出线粒体肌酸激酶2（Ckmt2）是再灌注AMI小鼠血浆中差异调节的蛋白质。再灌注AMI后，Ckmt2水平升高与梗死面积和LV功能受损显著相关，提示其特异性参与再灌注损伤。
我们的研究强调了血浆Ckmt2作为评估再灌注损伤及其对心肌梗死急性期心脏功能和形态影响的生物标志物的潜力。
