Adaptive strategies of the vertebrate heart to environmental stress; regulation of function and morphology

脊椎动物的心脏适应性非常强。这方面的一个例子是，当动物受到惊吓时，心脏收缩的速率和强度会迅速增加。另一个例子是心脏尺寸的增加，这是对长时间运动训练的反应。心脏功能和心脏形态的这些变化增加了血液输送到组织的速率，并使身体活动率更高。心脏也可能在心脏损伤或疾病后发生适应不良的变化。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。虽然上述适应性和适应不良的变化已经在器官水平上得到了很好的描述，但对启动和调节它们的细胞途径知之甚少。 拟议的研究项目侧重于调节心脏收缩的机制，以及那些驱动心脏形态和组成变化以应对心脏压力水平增加的机制。在第一组研究中，我们将确定特定收缩蛋白序列的差异如何与鳟鱼，青蛙和大鼠心脏的功能特性相关。我们将特别关注当动物受到惊吓时心脏功能增加的机制，以及物种之间的差异。为了研究调节心脏形态和组成的途径，我们将研究鳟鱼的心脏重塑。鳟鱼的心脏经历了显着的变化，心脏的大小和形态与冷驯化，我们最近发现，热驯化导致心脏结缔组织减少。这是第一次在任何动物中报道这种变化。表征这种现象背后的细胞通路将增加我们对脊椎动物心脏适应压力源的理解，并可能有助于开发控制心脏损伤患者结缔组织（瘢痕组织）形成的治疗方法。这些研究将为调节心脏功能和适应性的过程提供新的见解。

The vertebrate heart is incredibly adaptable. An example of this is the rapid increase in the rate and strength of cardiac contraction that occurs when an animal gets startled. Another example is the increase in heart size that occurs in response to prolonged periods of exercise training. These changes in heart function and heart morphology increase the rate at which blood can be delivered to the tissues and enable 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 that regulate cardiac contraction and those that drive the changes in cardiac morphology and composition in response to increased levels of stress on the heart. In the first set of studies we will determine how differences in the sequence of specific contractile proteins relate to the functional properties of trout, frog and rat hearts. We will specifically focus on the mechanisms responsible for the increase in cardiac function that occurs when an animal is scared and how this differs between species. To study the pathways that regulate the morphology and composition of the heart we will examine cardiac remodeling in trout. The trout heart undergoes significant changes in heart size and morphology with cold acclimation and we have recently found that warm acclimation causes a decrease in cardiac connective tissue. This is the first time that such a change has been reported in any animal. Characterizing the cellular pathways underlying this phenomenon will increase our understanding of what enables the vertebrate heart to adapt to stressors and may help develop treatments to control connective tissue (scar tissue) formation in patients who have suffered cardiac injury. Together these studies will provide novel insight into the processes that regulate cardiac function and adaptation.