Forkhead Box O in ischemia/reperfusion injury: a potential therapeutic target

Abstract

Acute myocardial infarction (AMI) is a major cause of morbidity. AMI is caused by a blockage of one or multiple coronary arteries, leading to an ischemic (loss of blood flow) area of the heart. Restoring blood flow (reperfusion) to the ischemic area is the primary course of action when an AMI patient presents himself. Reperfusion of the infarcted area however causes injury to the previously ischemic area, meaning that the treatment itself is damaging to the myocardium. This damaging period is termed ischemia/reperfusion injury and the proposed processes propagating I/R injury will be described in this paper. Forkhead Box O (FOXO) family of transcription factors are regulators of many genes involved in processes like reactive oxygen species (ROS) scavenging, apoptosis, development and immunity. Almost all of the functions which can be exerted by FOXOs via their target genes can be related to I/R injury, as will be discussed in this paper. The primary goal of this paper is to give the reader better insight into the processes underlying I/R injury, and the functions and regulation of FOXOs. Can and should FOXOs, considering their numerous target genes, be targeted therapeutically to attenuate ischemia/reperfusion injury?