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Adult Zebrafish Hearts Efficiently Compensate for Excessive Forced Overload Cardiac Stress with Hyperplastic Cardiomegaly

机译:成年斑马鱼心脏可有效补偿过度增生性心脏肥大引起的过度强迫心脏负荷

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Although human cardiomyocytes (CMs) are capable of some cell division, this response is neither sufficient to repair damaged cardiac tissue nor efficient to compensate for pathological stress. Danio rerio (zebrafish) CMs have been shown to have high proliferative capability to completely repair hearts after injury; however, no reports have focused on their physiological and cellular response to cardiac overload stress. We hypothesized that forced excessive long-term cardiac overload stress would elicit a proliferative response similar to regenerative cardiac repair in zebrafish. We completed a 10-week forced fast-speed swimming exercise regimen, comparing exercised hearts to nonexercised controls for physiological function and histological evidence of cell proliferation. Our results indicate that exercised heart ventricles are 33% larger, yet exhibit no significant changes in cardiac physiological function as evaluated by the heart rate and the percent shortening fraction. We found 8% more CM nuclei per cross-sectional area within exercised ventricular tissue, indicating that cardiomegaly was not due to individual cell hypertrophy, but due to hyperplasia. This novel zebrafish cardiac stress model may be used to identify genes or proteins with therapeutic potential for treating cardiac stress pathologies, as well as molecules that could be used as initiators of cardiac cell proliferation in humans.
机译:尽管人心肌细胞(CMs)能够进行某些细胞分裂,但这种反应既不足以修复受损的心脏组织,也不足以补偿病理应激。斑马鱼(Danio rerio)(斑马鱼)CM具有很高的增生能力,可以在受伤后完全修复心脏。然而,没有报道集中于它们对心脏超负荷应激的生理和细胞反应。我们假设强迫过度的长期心脏超负荷应激会引起类似于斑马鱼再生心脏修复的增殖反应。我们完成了一个为期10周的强制快速游泳运动方案,将运动过的心脏与未经锻炼的对照进行了生理功能和细胞增殖的组织学比较。我们的结果表明,经心率和缩短百分率评估,运动过的心室增大了33%,但心脏生理功能没有明显变化。我们发现运动心室组织内每横截面积的CM核多8%,这表明心脏肥大不是由于单个细胞肥大,而是由于增生。这种新颖的斑马鱼心脏应激模型可用于鉴定具有治疗心脏应激病理的治疗潜力的基因或蛋白质,以及可用作人类心脏细胞增殖引发剂的分子。

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