ABSTRACT
Numerous biological processes are associated with myocardial ischemia and reperfusion injury. These include the activation of cell death programmes (necrosis, apoptosis, and autophagy), innate and adaptive immune responses, myobrilar hypercontracture, pH and metabolic disruption, and microvascular permeability and leakage. Therapeutic approaches aimed at targeting the biological cascade associated with reperfusion injury have involved ischemic pre-and postconditioning, activation of the reperfusion injury salvage kinase (RISK) pathway, and targeting the mitochondrial transition pore PTP. Given the involvement of reactive oxygen species (ROS) in reperfusion injury, antioxidants have also been widely investigated as potential therapeutic
3.1 Introduction ............................................................................................................................ 35 3.2 Myocardial Ischemia and Reperfusion Injury ........................................................................36 3.3 Pathobiology of Vascular Reperfusion Injury and Therapies ................................................. 37
3.3.1 Mediators of Reperfusion Injury ................................................................................ 39 3.3.1.1 Oxidative Stress ...........................................................................................40 3.3.1.2 Physiological pH ..........................................................................................40 3.3.1.3 Inammation ................................................................................................40 3.3.1.4 Mitochondrial PTP ...................................................................................... 41
3.3.2 Ischemic Postconditioning and Preconditioning ........................................................ 41 3.3.3 RISK Pathway ............................................................................................................. 41
3.4 Genetic Alterations in Ischemia and Reperfusion Injury ....................................................... 42 3.5 Epigenetic Mechanisms in Ischemia and Reperfusion Injury ................................................ 43
3.5.1 Epigenetic Therapies ...................................................................................................44 3.6 Dietary Antioxidants in Ischemia and Reperfusion Injury ....................................................46 3.7 Conclusion .............................................................................................................................. 49 Acknowledgments ............................................................................................................................ 49 References ........................................................................................................................................ 49
agents. In this chapter, we discuss recent advances in our understanding of the molecular basis of myocardial ischemia and reperfusion injury. Genetic events are analyzed and emerging epigenetic mechanisms are described in the context of potential therapeutics. Already, numerous synthetic and dietary chromatin-modifying compounds have been investigated in models of disease. We discuss the mechanisms of action of dietary and synthetic antioxidants and chromatin-modifying compounds in detail.
