Abstract
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 weeks old) were used. Following pretreatment with or without thiamine pyrophosphate (TPP; 300 mM), 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 TPP-treated heart was significantly higher than that in untreated heart. Metabolome analysis was performed using capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS), and it revealed that TPP-treated heart retained higher adenosine triphosphate (ATP) levels compared with untreated heart after ischemia. The metabolic pathway showed that there was a significant increase in fumaric acid and malic acid from the tricarboxylic acid (TCA) cycle following ischemia. Electron microscope analysis revealed that the mitochondria size in TPP-treated heart was larger than that in untreated heart. Mitochondrial fission in TPP-treated heart was also inhibited, which was confirmed by a decrease in the phosphorylation level of DRP1. TPP treatment for cardiac ischemia preserved ATP levels probably as a result of maintaining larger mitochondria by inhibiting fission, thereby allowing TPP-treated heart to preserve contractility performance during reperfusion.
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