Mechanisms of change, cellular responses of the fish heart to physiological stress

鱼心脏对生理应激的变化机制、细胞反应

• 批准号: RGPIN-2017-06292
• 负责人: Gillis, Todd
• 金额: $ 2.84万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=757626
• 关键词: Mechanisms; change; cellular; responses; fish

A powerful heart is essential to supporting life. Interesting, the vertebrate heart is able to change both its form and function to meet the changing requirements of the animal. For example, exercise training will cause the heart to increase in size and pump more blood per beat. This change to the heart increases the rate at which blood can be delivered to the tissues and enables a higher rate of physical activity. The heart can also undergo maladaptive changes following cardiac injury or disease. Here, scar tissue forms in the heart and the amount of muscle decreases resulting in a weakened heart with impaired function. While the above adaptive and maladaptive changes have been well described at the organ level, there is less known of the cellular pathways responsible for initiating and regulating them. The proposed research project is focused on the mechanisms responsible for controlling changes in the structure and functional capacity of the vertebrate heart. We will specifically examine the remodeling response of the trout heart and zebrafish heart to a change in temperature and the ability of the hagfish heart to function without oxygen. The hearts of these fish species are very good models to examine cardiac remodeling as they can maintain function across a significant range of physiological conditions and also function under conditions that would stop the human heart. In the first study we will examine the ability of the trout heart and zebrafish heart to manipulate collagen content in response to a change in environmental temperature. In humans, a build-up of collagen can lead to heart failure as the heart becomes stiff and unable to relax between beats. Knowledge gained by characterizing the cellular pathways that regulate collagen deposition in the hearts of fish may help in developing treatments to control connective tissue formation in patients who have suffered cardiac injury. Cold acclimation of trout also causes the heart muscle to generate more force. In the second study we will examine how the cellular machinery changes with cold acclimation and see if we can reproduce this response in warm acclimated fish hearts. Finally, in a recent study we have demonstrated the hagfish heart can maintain function without oxygen for more than 16 h. This is an amazing ability considering that the human heart begins to die within minutes of oxygen deprivation. In the third study, we will determine the cellular mechanism(s) that enable the hagfish heart to power contraction without oxygen. Such knowledge has application in the development of strategies to preserve heart tissue following a heart attack or during transplant. Together these studies will provide novel insight into the processes that regulate cardiac function and adaptation.

强大的心脏对维持生命至关重要。有趣的是，脊椎动物的心脏能够改变它的形状和功能，以满足动物不断变化的需求。例如，运动训练会使心脏增大，每跳泵出更多的血。心脏的这种变化增加了血液输送到组织的速度，并使身体活动的速度更快。心脏也可能在心脏损伤或疾病后发生不适应变化。在这里，疤痕组织在心脏中形成，肌肉数量减少，导致心脏功能受损。虽然上述适应和不适应的变化已经在器官水平上得到了很好的描述，但对负责启动和调节它们的细胞途径知之甚少。拟开展的研究项目主要关注脊椎动物心脏结构和功能变化的控制机制。我们将特别研究鳟鱼心脏和斑马鱼心脏对温度变化的重塑反应，以及盲鳗心脏在缺氧情况下的功能。这些鱼类的心脏是研究心脏重塑的很好的模型，因为它们可以在很大范围的生理条件下保持功能，也可以在人类心脏停止的条件下工作。在第一项研究中，我们将研究鳟鱼心脏和斑马鱼心脏在环境温度变化下调节胶原蛋白含量的能力。在人类中，胶原蛋白的积累会导致心脏衰竭，因为心脏会变得僵硬，在心跳之间无法放松。通过描述调节鱼类心脏胶原沉积的细胞途径所获得的知识，可能有助于开发控制心脏损伤患者结缔组织形成的治疗方法。鳟鱼在寒冷环境中的适应也会使心脏肌肉产生更多的力量。在第二项研究中，我们将研究细胞机制如何随着冷环境的变化而变化，并看看我们是否可以在温暖环境下的鱼心脏中复制这种反应。最后，在最近的一项研究中，我们已经证明盲鳗的心脏可以在没有氧气的情况下维持16小时以上的功能。考虑到人类的心脏在缺氧的几分钟内就开始死亡，这是一种惊人的能力。在第三项研究中，我们将确定使盲鳗心脏在没有氧气的情况下收缩的细胞机制。这些知识在心脏病发作后或移植期间保护心脏组织的策略发展中具有应用价值。总之，这些研究将为调节心脏功能和适应的过程提供新的见解。