Humanin exerts cardioprotection against cardiac ischemia/reperfusion injury through attenuation of mitochondrial dysfunction

• Published in: Cardiovascular therapeutics Vol. 34; no. 6; pp. 404 - 414
• Main Authors: Thummasorn, Savitree, Apaijai, Nattayaporn, Kerdphoo, Sasiwan, Shinlapawittayatorn, Krekwit, Chattipakorn, Siriporn C., Chattipakorn, Nipon
• Format: Journal Article
• Language: English
• Published: England Hindawi Limited 01.12.2016
• Subjects: Animals; Apoptosis; Arrhythmias, Cardiac - physiopathology; Arrhythmias, Cardiac - prevention & control; Cardiac arrhythmia; Cardiotonic Agents - administration & dosage; Disease Models, Animal; Drug Administration Schedule; Heart; Humanin; Intracellular Signaling Peptides and Proteins - administration & dosage; Ischemia; Ischemia/reperfusion injury; Male; Mitochondria, Heart - drug effects; Mitochondria, Heart - metabolism; Mitochondria, Heart - pathology; Mitochondrial Diseases - metabolism; Mitochondrial Diseases - pathology; Mitochondrial Diseases - physiopathology; Mitochondrial Diseases - prevention & control; Mitochondrial DNA; Mitochondrial dysfunction; Myocardial Infarction - metabolism; Myocardial Infarction - pathology; Myocardial Infarction - physiopathology; Myocardial Infarction - prevention & control; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - physiopathology; Myocardial Reperfusion Injury - prevention & control; Myocardium - metabolism; Myocardium - pathology; Oxidative stress; Oxidative Stress - drug effects; Rats, Wistar; Reactive Oxygen Species - metabolism; Time Factors; Ventricular Function, Left - drug effects; Heart; Oxidative stress; Ischemia/reperfusion injury; Mitochondrial dysfunction; Humanin; Apoptosis
• ISSN: 1755-5914; 1755-5922
• DOI: 10.1111/1755-5922.12210

Summary Aim Myocardial reperfusion via the re‐canalization of occluded coronary arteries is gold standard for the treatment of acute myocardial infarction. However, reperfusion itself can cause myocardial damage due to increased reactive oxygen species (ROS) production, a process known as ischemia/reperfusion (I/R) injury. Cardiac mitochondria are the major organelle of ROS production in the heart. Cardiac mitochondrial dysfunction caused by an increased ROS production can increase cardiac arrhythmia incidence, myocardial infarct size, and cardiac dysfunction. Thus, preservation of cardiac mitochondrial function is a promising pharmacological approach to reduce cardiac I/R injury. Humanin (HN), a newly discovered 24‐amino acid polypeptide, has been shown to exert antioxidative stress and antiapoptotic effects. Although the cardioprotective effects of HN against I/R injury has been reported, the effect of HN on cardiac mitochondrial function has not yet been investigated. Thus, we tested the hypothesis that HN exerts its cardioprotective effects against I/R injury through the attenuation of cardiac mitochondrial dysfunction. Methods I/R protocol was carried out using a 30‐minutes occlusion of a left anterior descending coronary artery followed by a 120‐minutes of reperfusion. The plasma HN level, infarct size, arrhythmia incidence, left ventricular function, and cardiac mitochondrial function were determined. Results Endogenous HN level before I/R injury showed no difference between groups, but was markedly decreased after I/R injury. HN analogue pretreatment decreased arrhythmia incidence and infarct size, improved cardiac mitochondrial function, and attenuated cardiac dysfunction. Conclusions Humanin analogue pretreatment exerted cardioprotective effects against I/R injury through the attenuation of cardiac mitochondrial dysfunction.