humanin and Myocardial-Infarction

Humanin is an endogenous mitochondria-derived peptide that plays critical roles in oxidative stress, inflammation and CAD. In this study, we measured the levels of circulating humanin, markers of oxidative stress and inflammation in patients with unstable angina and MI and studied the relationship between these parameters and major adverse cardiac events (MACE).. A total of 327 subjects were recruited from the inpatient department at First Hospital of Jilin University and divided into 3 groups [control, angina and myocardial infarction (MI)] based on the clinical data and the results of the angiography. Serum humanin and thiobarbituric acid reactive substances (TBARS) were measured at the time of initial admission. The hospitalization data and MACE of all patients were collected.. Circulating humanin levels were lower in the angina group compared to controls [124.22 ± 63.02 vs. 157.77 ± 99.93 pg/ml, p < 0.05] and even lower in MI patients [67.17 ± 24.35 pg/ml, p < 0.05 vs controls] and oxidative stress marker were higher in MI patients compared to the control and angina groups [12.94 ± 4.55 vs. 8.26 ± 1.66 vs. 9.06 ± 2.47 umol/ml, p < 0.05]. Lower circulating humanin levels was an independent risk factor of MI patients. Circulating humanin levels could be used to predict MACE in angina group.. Lower circulating humanin levels was an independent risk factor for CAD, and a potential prognostic marker for mild CAD.. Humanin may become a new index for the diagnosis and treatment of CAD.

Topics: Adult; Angina Pectoris; Biomarkers; Coronary Artery Disease; Female; Heart; Humans; Inflammation; Intracellular Signaling Peptides and Proteins; Male; Middle Aged; Mitochondria; Myocardial Infarction; Oxidative Stress; Prognosis; Risk Factors

Although the gold standard treatment for acute myocardial infarction is reperfusion therapy, reperfusion itself can cause myocardial damage via induction of cardiac mitochondrial dysfunction. This can lead to increased myocardial infarct size, arrhythmias, and left ventricular (LV) dysfunction. Recently, a newly discovered peptide, Humanin, has been shown to exert several beneficial effects including antioxidative and antiapoptosis effects. We recently reported that a Humanin analogue (HNG, 84 μg/kg) given prior to cardiac ischemia exerted cardioprotection against I/R injury, but failed to do so when it was given after ischemia was induced. However, in a clinical setting, patients can only be treated after the onset of ischemia. In this study, we investigated the potential benefit of various doses of HNG therapy (84, 168, 252 μg/kg) against myocardial I/R injury when applied during ischemia on cardiac arrhythmia, myocardial infarct size, cardiac mitochondrial function, and LV function.. Myocardial I/R injury was induced in rats by 30-minute left anterior descending coronary artery occlusion, followed by 120-minute of reperfusion. HNG at the different doses were given intravenously at 15 minutes after ischemic onset and also at the onset of reperfusion.. HNG (252 μg/kg) applied during the ischemic period not only increased HN levels in the damaged myocardium, but also significantly decreased cardiac arrhythmia, myocardial infarct size, cardiac mitochondrial dysfunction, and left ventricular dysfunction. These benefits were mediated through the attenuation of cardiac mitochondrial dysfunction.. High-dose HN applied during ischemia in rats could exert cardioprotection against I/R injury-induced mitochondrial dysfunction.

Topics: Animals; Arrhythmias, Cardiac; Disease Models, Animal; Dose-Response Relationship, Drug; Intracellular Signaling Peptides and Proteins; Male; Mitochondria, Heart; Myocardial Infarction; Myocardial Reperfusion Injury; Myocytes, Cardiac; Protective Agents; Rats, Wistar; Signal Transduction; Ventricular Function, Left

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.. 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.. 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.. Humanin analogue pretreatment exerted cardioprotective effects against I/R injury through the attenuation of cardiac mitochondrial dysfunction.

Topics: Animals; Arrhythmias, Cardiac; Cardiotonic Agents; Disease Models, Animal; Drug Administration Schedule; Intracellular Signaling Peptides and Proteins; Male; Mitochondria, Heart; Mitochondrial Diseases; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Oxidative Stress; Rats, Wistar; Reactive Oxygen Species; Time Factors; Ventricular Function, Left