• Cellular and Molecular Dynamics of Stressed Myocardium

      Riley, Dushon; Lederer, W. Jonathan (2014)
      All organisms will be exposed to various types of stress throughout their lifetimes. These can range from exogenous toxins to extreme temperatures and have the potential to destabilize proper cellular function. Cells have adapted ways to respond to various types of stress and do so in an attempt to maintain or reestablish cellular homeostasis. This is especially true of the heart as it must perform its function continuously and consistently throughout the entire lifespan of an organism. The work reported here investigates the effects of stress on the dynamics of heart muscle function. Three models of stress are investigated: (1) acute inflammatory stress, (2) constitutive mitochondrial stress and (3) hyperglycemic stress. By using fluorescent confocal microscopy, immunohistochemistry and digital image processing, I examined the effects of acute inflammatory stress on Ca2+ signaling in neonatal cardiac myocytes. I also explored the therapeutic potential of stem cells in an inflammation paradigm showing that they can elicit both a protective and reparative effect in an inflammation model. I also examined Ca2+ dynamics and mitochondrial membrane potential stability in adult cardiac myocytes in a model of mitochondrial stress. In this model, I explored the role of mitofusin 2 in the ability of the mitochondrial membrane to resist depolarization as well as its effects on Ca2+ transients and myocyte contraction. Finally, I investigated the effects of acute hyperglycemia on mitochondrial membrane resistance to depolarization and alteration of oxidative state within the cell. This work demonstrates how the heart muscle responds to various environmental stressors and lays the foundation for further exploration into not only these specific stress models but the cardiac cell stress response. We discovered that multiple pathways are involved in the cellular response to stress in heart, often in conjunction with each other. This linkage of stress related pathways in heart should yield fruitful avenues of research for the future.