The Role of Mitochondrial Reactive Oxygen Species in Cardiovascular Injury and Protective Strategies

Abstract

Ischaemia/reperfusion (I/R) injury of the heart represents a major health burden mainly associated with acute coronary syndromes. While timely coronary reperfusion has become the established routine therapy in patients with ST-elevation myocardial infarction, the restoration of blood flow into the previously ischaemic area is always accompanied by myocardial injury. The central mechanism involved in this phenomenon is represented by the excessive generation of reactive oxygen species (ROS). Besides their harmful role when highly generated during early reperfusion, minimal ROS formation during ischaemia and/or at reperfusion is critical for the redox signaling of cardioprotection. In the past decades, mitochondria have emerged as the major source of ROS as well as a critical target for cardioprotective strategies at reperfusion. Mitochondria dysfunction associated with I/R myocardial injury is further described and ultimately analyzed with respect to its role as source of both deleterious and beneficial ROS. Furthermore, the contribution of ROS in the highly investigated field of conditioning strategies is analyzed. In the end, the vascular sources of mitochondria-derived ROS are briefly reviewed.

Reactive oxygen species: key regulators in vascular health and diseases

“…However, under pathological conditions, dysfunctional uncoupled eNOS no longer produces NO, but O 2 •− , which aggravates oxidative stress (Forstermann and Sessa, ; Li and Forstermann, ). Besides enzymic sources of ROS, the mitochondrial respiratory electron transport chain (ETC), which is another important source of harmful ROS, serves as a key generator in atherosclerosis and heart diseases (Li et al, ; Muntean et al, ). Mitochondria are responsible for utilizing oxygen for energy production and oxidative phosphorylation.…”

DJ‐1 plays an obligatory role in the cardioprotection of delayed hypoxic preconditioning against hypoxia/reoxygenation‐induced oxidative stress through maintaining mitochondrial complex I activity

“…It is well established that increased reactive oxygen species (ROS) and subsequent oxidative stress are one of the major causes of myocardial I/R injury, whereas a potential source of ROS generation is thought to be the mitochondrial respiratory chain . It has now been recognized that mitochondrial complex I is a main site of ROS production in mitochondria . Experimental evidence has shown that impairment of mitochondrial complex I activity by I/R increases the electron leakage by blocking the electron transfer at complex I and leads to ROS overproduction that ultimately induces a vicious cycle of oxidative stress .…”

Association between ROS production, swelling and the respirasome integrity in cardiac mitochondria

“…Increases in cellular Ca 2+ and reactive oxygen species (ROS) induced by ischemia and then, amplified upon reperfusion are the main mediators of reperfusion injury [2]. Mitochondria have emerged as the major source of ROS as well as a critical target for cardioprotective strategies at reperfusion [3]. Mitochondrial Ca 2+ overload accompanied by oxidative stress and increased Pi levels leads to mitochondrial permeability transition (PT) accompanied by opening non-selective PT pores (PTP) in the inner mitochondrial membrane.…”