Adipose-derived mesenchymal stromal cell (AD-MSC) administration improves cardiac function after acute myocardial infarction (AMI). Although the mechanisms underlying this effect remain to be elucidated, the reversal of the mitochondrial dysfunction may be associated with AMI recovery. Here, we analyzed the alterations in the respiratory capacity of cardiomyocytes in the infarcted zone (IZ) and the border zone (BZ) and evaluated if mitochondrial function improved in cardiomyocytes after AD-MSC transplantation. Female rats were subjected to AMI by permanent left anterior descending coronary (LAD) ligation and were then treated with AD-MSCs or PBS in the border zone (BZ). Cardiac fibers were analyzed 24 hours (necrotic phase) and 8 days (fibrotic phase) after AMI for mitochondrial respiration, citrate synthase (CS) activity, F₀F₁-ATPase activity, and transmission electron microscopy (TEM). High-resolution respirometry of permeabilized cardiac fibers showed that AMI reduced numerous mitochondrial respiration parameters in cardiac tissue, including phosphorylating and nonphosphorylating conditions, respiration coupled to ATP synthesis, and maximal respiratory capacity. CS decreased in IZ and BZ at the necrotic phase, whereas it recovered in BZ and continued to drop in IZ over time when compared to Sham. Exogenous cytochrome c doubled respiration at the necrotic phase in IZ. F₀F₁-ATPase activity decreased in the BZ and, to more extent, in IZ in both phases. Transmission electron microscopy showed disorganized mitochondrial cristae structure, which was more accentuated in IZ but also important in BZ. All these alterations in mitochondrial respiration were still present in the group treated with AD-MSC. In conclusion, AMI led to mitochondrial dysfunction with oxidative phosphorylation disorders, and AD-MSC improved CS temporarily but was not able to avoid alterations in mitochondria function over time.

中文翻译：

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尽管有脂肪组织间质基质细胞移植，急性心肌梗塞仍可降低大鼠心脏纤维的呼吸。

脂肪来源的间充质基质细胞（AD-MSC）给药可改善急性心肌梗塞（AMI）后的心脏功能。尽管该作用的机制尚待阐明，但线粒体功能障碍的逆转可能与AMI恢复有关。在这里，我们分析了梗死区（IZ）和边界区（BZ）中心肌细胞呼吸能力的变化，并评估了AD-MSC移植后心肌细胞的线粒体功能是否得到改善。雌性大鼠通过永久性左前冠状动脉前降支（LAD）结扎进行AMI，然后在边界区（BZ）中用AD-MSC或PBS治疗。在AMI后24小时（坏死期）和8天（纤维化期）分析心脏纤维的线粒体呼吸作用，柠檬酸合酶（CS）活性，F₀ F ₁ -ATPase活性和透射电子显微镜（TEM）。透化心脏纤维的高分辨率呼​​吸测定法显示，AMI降低了心脏组织中许多线粒体呼吸参数，包括磷酸化和非磷酸化条件，与ATP合成相关的呼吸作用以及最大的呼吸能力。与假手术相比，在坏死期，IZ和BZ中的CS下降，而在BZ中恢复，并且IZ随时间持续下降。在IZ的坏死阶段，外源性细胞色素c使呼吸增加了一倍。F ₀ F ₁在两个阶段中，BZ中的-ATPase活性均下降，并且在IZ中的程度更大。透射电子显微镜显示线粒体的ista结构杂乱无章，在IZ中更为突出，但在BZ中也很重要。线粒体呼吸的所有这些改变仍存在于用AD-MSC治疗的组中。总之，AMI导致线粒体功能障碍并伴有氧化磷酸化障碍，AD-MSC暂时改善CS，但无法避免线粒体功能随时间的变化。