Mitochondrial Dysfunction and Myocardial Ischemia-Reperfusion: Implications for Novel Therapies

Abstract

Mitochondria have emerged as key participants in and regulators of myocardial injury during ischemia and reperfusion. This review examines the sites of damage to cardiac mitochondria during ischemia and focuses on the impact of these defects. The concept that mitochondrial damage during ischemia leads to cardiac injury during reperfusion is addressed. The mechanisms that translate ischemic mitochondrial injury into cellular damage, during both ischemia and early reperfusion, are examined. Next, we discuss strategies that modulate and counteract these mechanisms of mitochondrial-driven injury. The new concept that mitochondria are not merely stochastic sites of oxidative and calcium-mediated injury but that they activate cellular responses of mitochondrial remodeling and cellular reactions that modulate the balance between cell death and recovery is reviewed, and the therapeutic implications of this concept are discussed.

Amifostine Pretreatment Attenuates Myocardial Ischemia/Reperfusion Injury by Inhibiting Apoptosis and Oxidative Stress

“…This is a complicated process including numerous mechanisms occurring in the intracellular and extracellular environments, and part of that is mediated by ROS [20]. ROS can be produced from several major sources, like cytochrome oxidase, unsaturated fatty acid oxidation, mitochondrial oxidation, and so on.…”

The relationship between phospholipids and insulin resistance: From clinical to experimental studies

“…Unlike other abundant phospholipids, cardiolipin is exclusively localized to the mitochondria . Most studies have focused on the role of cardiolipin in regulating mitochondrial function . Changes in cardiolipin content as well as its fatty acid composition have been observed in models of diabetes.…”

Metabolism of hyperpolarized 13C‐acetoacetate to β‐hydroxybutyrate detects real‐time mitochondrial redox state and dysfunction in heart tissue

“…Mitochondria are recognized as crucial targets and regulators of cardiac injury during ischemia and reperfusion . The role of mitochondria is essential in metabolism and maintaining energy homeostasis as they synthesize the majority of ATP and biosynthetic intermediates needed for cell growth and function.…”

“…Mitochondria are recognized as crucial targets and regulators of cardiac injury during ischemia and reperfusion. 1 The role of mitochondria is essential in metabolism and maintaining energy homeostasis as they synthesize the majority of ATP and biosynthetic intermediates needed for cell growth and function. Dysfunctional mitochondria and impaired energy homeostasis are intricately linked with heart failure and several other high impact diseases including type 2 diabetes, cancer, and neurodegenerative diseases.…”