Basic Research in Cardiology ( IF 7.5 ) Pub Date : 2024-03-18 , DOI: 10.1007/s00395-024-01040-6 Sally Badawi 1, 2, 3 , Clémence Leboullenger 4 , Matthieu Chourrout 1, 5 , Yves Gouriou 1, 2 , Alexandre Paccalet 1, 2 , Bruno Pillot 1, 2 , Lionel Augeul 1, 2 , Radu Bolbos 6 , Antonino Bongiovani 4 , Nathan Mewton 1, 2, 7 , Thomas Bochaton 1, 2, 8 , Michel Ovize 1, 2 , Meryem Tardivel 4 , Mazen Kurdi 3 , Emmanuelle Canet-Soulas 1, 2 , Claire Crola Da Silva 1, 2 , Gabriel Bidaux 1, 2
Myocardial infarction (MI) is a serious acute cardiovascular syndrome that causes myocardial injury due to blood flow obstruction to a specific myocardial area. Under ischemic–reperfusion settings, a burst of reactive oxygen species is generated, leading to redox imbalance that could be attributed to several molecules, including myoglobin. Myoglobin is dynamic and exhibits various oxidation–reduction states that have been an early subject of attention in the food industry, specifically for meat consumers. However, rarely if ever have the myoglobin optical properties been used to measure the severity of MI. In the current study, we develop a novel imaging pipeline that integrates tissue clearing, confocal and light sheet fluorescence microscopy, combined with imaging analysis, and processing tools to investigate and characterize the oxidation–reduction states of myoglobin in the ischemic area of the cleared myocardium post-MI. Using spectral imaging, we have characterized the endogenous fluorescence of the myocardium and demonstrated that it is partly composed by fluorescence of myoglobin. Under ischemia–reperfusion experimental settings, we report that the infarcted myocardium spectral signature is similar to that of oxidized myoglobin signal that peaks 3 h post-reperfusion and decreases with cardioprotection. The infarct size assessed by oxidation–reduction imaging at 3 h post-reperfusion was correlated to the one estimated with late gadolinium enhancement MRI at 24 h post-reperfusion. In conclusion, this original work suggests that the redox state of myoglobin can be used as a promising imaging biomarker for characterizing and estimating the size of the MI during early phases of reperfusion.
中文翻译:
肌红蛋白的氧化还原成像显示再灌注心肌中的两相氧化
心肌梗死 (MI) 是一种严重的急性心血管综合征,由于特定心肌区域的血流阻塞而导致心肌损伤。在缺血再灌注设置下,会产生活性氧的爆发,导致氧化还原失衡,这可能归因于包括肌红蛋白在内的几种分子。肌红蛋白是动态的,表现出各种氧化还原态,这些态一直是食品工业的早期关注对象,特别是对于肉类消费者。然而,肌红蛋白光学特性很少(如果有的话)用于测量 MI 的严重程度。在目前的研究中,我们开发了一种新的成像管道,它集成了组织透明化、共聚焦和光片荧光显微镜,结合成像分析和处理工具,以研究和表征心肌梗死后清除心肌缺血区域中肌红蛋白的氧化还原态。使用光谱成像,我们表征了心肌的内源性荧光,并证明它部分由肌红蛋白的荧光组成。在缺血再灌注实验设置下,我们报道梗死心肌谱特征类似于氧化肌红蛋白信号的信号,该信号在再灌注后 3 小时达到峰值,并在心脏保护下降低。再灌注后 3 小时通过氧化还原成像评估的梗死面积与再灌注后 24 小时用晚期钆增强 MRI 估计的面积相关。总之,这项原始工作表明,肌红蛋白的氧化还原状态可以用作一种很有前途的成像生物标志物,用于表征和估计再灌注早期 MI 的大小。