Treatment of Oxidative Stress with Exosomes in Myocardial Ischemia

Abstract

A thrombus in a coronary artery causes ischemia, which eventually leads to myocardial infarction (MI) if not removed. However, removal generates reactive oxygen species (ROS), which causes ischemia–reperfusion (I/R) injury that damages the tissue and exacerbates the resulting MI. The mechanism of I/R injury is currently extensively understood. However, supplementation of exogenous antioxidants is ineffective against oxidative stress (OS). Enhancing the ability of endogenous antioxidants may be a more effective way to treat OS, and exosomes may play a role as targeted carriers. Exosomes are nanosized vesicles wrapped in biofilms which contain various complex RNAs and proteins. They are important intermediate carriers of intercellular communication and material exchange. In recent years, diagnosis and treatment with exosomes in cardiovascular diseases have gained considerable attention. Herein, we review the new findings of exosomes in the regulation of OS in coronary heart disease, discuss the possibility of exosomes as carriers for the targeted regulation of endogenous ROS generation, and compare the advantages of exosome therapy with those of stem-cell therapy. Finally, we explore several miRNAs found in exosomes against OS.

Stem Cell-Derived Exosomes Potential Therapeutic Roles in Cardiovascular Diseases

“…Arslan et al ( 163 ) showed that a single intravenous injection of exosomes (5 mm) before reperfusion reduced the size of infarct by ~45% in mice. It was also reported that the treatment with exosomes helped to restore depleted energy and redox rate potential in mouse health within 30 min after I/R, which was proven by the presence of increased levels of ATP and NADH levels with a decrease in oxidative stress ( 164 ). The studies conclude that MSC-derived exosomes harbor all necessary enzymes that are required for the generation of ATP ( 165 , 166 ).…”

Reactive oxygen species-based nanomaterials for the treatment of myocardial ischemia reperfusion injuries

“…Exosomes are nano-sized membrane vesicles derived from a variety of cell types, and are thought to act as important intermediate carriers for intracellular communication and material exchange [ [266] , [267] , [268] ]. Specially, Exosomes secreted by MSCs contain a complex cargo including various proteins and miRNAs with the potential to be a source of cardiac regeneration and resistance to oxidative stress.…”

“…Moreover, exosomes therapy avoids the defects of MSCs transplantation, such as low percentage of local engraftment and survival rate. MSCs-derived exosomes have been demonstrated their beneficial effects for myocardial ischemia reperfusion injury therapy [ [266] , [267] , [268] , [269] , [270] ]. For example, Liu et al found that MSCs-derived exosomes significantly reduced cardiomyocyte apoptosis and the myocardial infarct size by inducing cardiomyocytes autophagy via targeting AMPK and Akt pathway [ 267 ].…”

“…For example, Wang et al prepared miRNA-19a/19b-loaded exosomes for the treatment of myocardial infarction [ 271 ]. miRNA-19a/19b can induce the proliferation of cardiomyocytes and promote cardiac regeneration [ 266 ]. Therefore, encapsulation of miRNA-19a/19b into MSC-derived exosomes could effectively accumulate in the ischemic myocardium, and significantly improve cardiac functional recovery.…”

Protective Mechanism of Humanin Against Oxidative Stress in Aging-Related Cardiovascular Diseases

“…With the increase of an aging population, aging-related cardiovascular diseases (ACVDs) confer a heavy economic burden on society (1,2). Oxidative stress is involved in the pathogenesis of ACVD (3)(4)(5), such as atherosclerosis (6), myocardial infarction (7), and heart failure (8), by contributing to apoptosis, hypertrophy, and fibrosis. Oxidative phosphorylation in mitochondria is the main source of reactive oxygen species (ROS).…”