Thiamine treatment preserves cardiac function against ischemia injury via maintaining mitochondrial size and ATP levels
Thiamine treatment preserves cardiac function against ischemia injury via maintaining mitochondrial size and ATP levels
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硫胺素治疗通过维持线粒体大小和 ATP 水平来保护心脏功能免受缺血损伤
DOI：
10.1152/japplphysiol.00578.2020
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发表时间：
2021
影响因子：
3.3
通讯作者：
Minamisawa Susumu
中科院分区：
文献类型：
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作者：
Yamada Yuki;Kusakari Yoichiro;Akaoka Munetoshi;Watanabe Masato;Tanihata Jun;Nishioka Naritomo;Bochimoto Hiroki;Akaike Toru;Tachibana Toshiaki;Minamisawa Susumu
硫胺素（维生素B1）是能量产生所必需的，特别是在心脏中。最近的研究表明，补充硫胺素对心脏疾病是有益的。然而，硫胺素保护心脏功能的详细机制尚未阐明。为此，我们进行了功能分析，代谢组学分析和电子显微镜分析，以揭示通过补充硫胺素治疗缺血性心脏病来保护心脏功能的机制。使用雄性Sprague-Dawley大鼠（约10周龄）。在用或不用焦磷酸硫胺素（TPP; 300 μM）预处理后，将心脏暴露于缺血（40分钟的全脑缺血，随后60分钟的再灌注）。我们在整个方案中测量了左心室发展压（LVDP）。再灌注期间，TPP处理的心脏的LVDP显著高于未处理的心脏。使用毛细管电泳-飞行时间质谱法进行代谢物组分析，结果显示，与缺血后未处理的心脏相比，TPP处理的心脏保留了更高的三磷酸腺苷（ATP）水平。代谢途径表明，有一个显着的增加，富马酸和苹果酸从三羧酸循环缺血后。电子显微镜分析显示，在TPP处理的心脏线粒体的大小大于在未处理的心脏。TPP处理的心脏中的线粒体分裂也被抑制，这通过DRP 1（分裂相关蛋白）磷酸化水平的降低来证实。TPP治疗心肌缺血保存ATP水平可能是由于维持较大的线粒体通过抑制裂变，从而使TPP治疗的心脏，以保持再灌注过程中的收缩性能。新&值得注意的是，我们发现，治疗与硫胺素可以有心肌缺血的保护作用。硫胺素可能通过抑制DRP 1磷酸化和保存较大尺寸的线粒体和ATP浓度来介导线粒体分裂，从而在随后的再灌注状态期间产生更高的心肌收缩性能。
Thiamine (vitamin B1) is necessary for energy production, especially in the heart. Recent studies have demonstrated that thiamine supplementation for cardiac diseases is beneficial. However, the detailed mechanisms underlying thiamine-preserved cardiac function have not been elucidated. To this end, we conducted a functional analysis, metabolome analysis, and electron microscopic analysis to unveil the mechanisms of preserved cardiac function through supplementation with thiamine for ischemic cardiac disease. Male Sprague–Dawley rats (around 10 wk old) were used. Following pretreatment with or without thiamine pyrophosphate (TPP; 300 µM), hearts were exposed to ischemia (40 min of global ischemia followed by 60 min of reperfusion). We measured the left ventricle developed pressure (LVDP) throughout the protocol. The LVDP during reperfusion in the TPP-treated heart was significantly higher than that in the untreated heart. Metabolome analysis was performed using capillary electrophoresis–time-of-flight mass spectrometry, and it revealed that the TPP-treated heart retained higher adenosine triphosphate (ATP) levels compared with the untreated heart after ischemia. The metabolic pathway showed that there was a significant increase in fumaric acid and malic acid from the tricarboxylic acid cycle following ischemia. Electron microscope analysis revealed that the mitochondria size in the TPP-treated heart was larger than that in the untreated heart. Mitochondrial fission in the TPP-treated heart was also inhibited, which was confirmed by a decrease in the phosphorylation level of DRP1 (fission related protein). TPP treatment for cardiac ischemia preserved ATP levels probably as a result of maintaining larger mitochondria by inhibiting fission, thereby allowing the TPP-treated heart to preserve contractility performance during reperfusion.NEW & NOTEWORTHYWe found that treatment with thiamine can have a protective effect on myocardial ischemia. Thiamine likely mediates mitochondrial fission through the inhibition of DRP1 phosphorylation and the preservation of larger-sized mitochondria and ATP concentration, leading to higher cardiac contractility performance during the subsequent reperfusion state.