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: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=712157
• 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。