Therapeutic Peptides to Treat Myocardial Ischemia-Reperfusion Injury

Abstract

Cardiovascular diseases (CVD) including acute myocardial infarction (AMI) rank first in worldwide mortality and according to the World Health Organization (WHO), they will stay at this rank until 2030. Prompt revascularization of the occluded artery to reperfuse the myocardium is the only recommended treatment (by angioplasty or thrombolysis) to decrease infarct size (IS). However, despite beneficial effects on ischemic lesions, reperfusion leads to ischemia-reperfusion (IR) injury related mainly to apoptosis. Improvement of revascularization techniques and patient care has decreased myocardial infarction (MI) mortality however heart failure (HF) morbidity is increasing, contributing to the cost-intense worldwide HF epidemic. Currently, there is no treatment for reperfusion injury despite promising results in animal models. There is now an obvious need to develop new cardioprotective strategies to decrease morbidity/mortality of CVD, which is increasing due to the aging of the population and the rising prevalence rates of diabetes and obesity. In this review, we will summarize the different therapeutic peptides developed or used focused on the treatment of myocardial IR injury (MIRI). Therapeutic peptides will be presented depending on their interacting mechanisms (apoptosis, necroptosis, and inflammation) reported as playing an important role in reperfusion injury following myocardial ischemia. The search and development of therapeutic peptides have become very active, with increasing numbers of candidates entering clinical trials. Their optimization and their potential application in the treatment of patients with AMI will be discussed.

Proteomics Revealed That Mitochondrial Function Contributed to the Protective Effect of Herba Siegesbeckiae Against Cardiac Ischemia/Reperfusion Injury

“…Percutaneous coronary intervention is the main effective strategy to treat acute coronary syndrome (ACS) by recovering myocardial perfusion, which can save patients’ lives to a certain extent ( 1 ). However, the mortality due to ACS has not been reduced, mainly due to myocardial ischemia/reperfusion (I/R) injury and subsequent myocardial fibrosis and heart failure ( 2 ). Though the significance of conquering I/R has been recognized for decades, there are currently only a few effective therapeutic interventions applied in a clinical setting to prevent I/R ( 3 ).…”

Modification of Ischemia/Reperfusion-Induced Alterations in Subcellular Organelles by Ischemic Preconditioning

“…Furthermore, the effects of IP on some factors, such as inflammatory cytokines and proteolytic activities, as well as the nuclear factor erythroid factor 2 (Nrf2) signal transduction pathway, which are known to modulate subcellular defects due to I/R injury, will be outlined. The generation of reactive oxygen species (ROS) and subsequent oxidative stress is known to increase apoptosis [ 24 ], necrosis [ 24 , 25 ], inflammation [ 24 ] and impair mitochondrial function [ 26 , 27 ]. In fact, IP has been demonstrated to attenuate the I/R-induced defects [ 28 , 29 , 30 , 31 ].…”

M2 macrophage-derived exosomal miR-145-5p protects against the hypoxia/reoxygenation-induced pyroptosis of cardiomyocytes by inhibiting TLR4 expression

“…Myocardial infarction, due to ischemia of the coronary vessels, leads to myocardial necrosis, and eventually heart failure and sudden death ( 3 ). Recently, research has shown ( 4 ) that prompt thrombolysis, percutaneous coronary intervention, and revascularization can save the infarcted myocardium and slow the course of the disease. However, blood supply restoration is accompanied by complex pathophysiological processes, including inflammatory factor release, oxidative stress, endothelial cell dysfunction, and energy metabolism imbalance, which can lead to myocardial tissue reperfusion injury ( 5 , 6 ).…”