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Collagenolytic Activity Is Associated with Scar Resolution in Zebrafish Hearts after Cryoinjury

机译:低温损伤后斑马鱼心脏中的胶原分解活性与疤痕消除有关。

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Myocardial infarction is the major cause of cardiac injury in western countries and can result in a massive loss of heart cells, leading eventually to heart failure. A fibrotic collagen-rich scar may prevent ventricular wall rupture, but also may result in heart failure because of its stiffness. In zebrafish, cardiac cryoinjury triggers a fibrotic response and scarring. Unlike with mammals, zebrafish heart has the striking ability to regenerate and to resolve the scar. Thus, understanding the mechanisms of scar resolution in zebrafish heart might facilitate the design of new therapeutic approaches to improve the recovery of patients. To visualize the collagenolytic activity within the zebrafish heart following cryoinjury, we used an in situ collagen zymography assay. We detected expression of mmp2 and mmp14a and these matrix metalloproteinases might contribute to the collagenase activity. Collagenolytic activity was present in the wound area, but decreased as the myocardium regenerated. Comparison with neonatal mouse hearts that failed to regenerate after transmural cryoinjury revealed a similar collagenolytic activity in the scar. These findings suggest that collagenolytic activity may be key to how the zebrafish heart resolves its scar; however, it is not sufficient in mouse hearts that lack efficient myocardial regeneration.
机译:在西方国家,心肌梗塞是造成心脏损伤的主要原因,并可导致心脏细胞大量丢失,最终导致心力衰竭。富含纤维化胶原蛋白的瘢痕可预防心室壁破裂,但由于其僵硬也可能导致心力衰竭。在斑马鱼中,心脏冷冻损伤会触发纤维化反应和瘢痕形成。与哺乳动物不同,斑马鱼的心脏具有惊人的再生能力和消除疤痕的能力。因此,了解斑马鱼心脏中疤痕消退的机制可能有助于设计新的治疗方法以改善患者的康复。为了可视化冷冻损伤后斑马鱼心脏内的胶原蛋白水解活性,我们使用了原位胶原酶谱测定法。我们检测到mmp2和mmp14a的表达,这些基质金属蛋白酶可能有助于胶原酶的活性。胶原蛋白水解活性存在于伤口区域,但随着心肌再生而降低。与经壁冷冻伤后无法再生的新生小鼠心脏进行比较,发现疤痕具有类似的胶原蛋白水解活性。这些发现表明胶原蛋白水解活性可能是斑马鱼心脏如何解决其疤痕的关键。但是,这在缺乏有效心肌再生的小鼠心脏中是不够的。

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