Dual Behavior of Exosomes in Septic Cardiomyopathy

Abstract

Sepsis is one of the main causes of ICU hospitalization worldwide, with a high mortality rate, and is associated with a large number of comorbidities. One of the main comorbidities associated with sepsis is septic cardiomyopathy. This process occurs mainly due to mechanisms of damage in the cardiovascular system that will lead to changes in cardiovascular physiology, such as decreased Ca response, mitochondrial dysfunction and decreased β-adrenergic receptor response. Within this process the exosomes play an important role in the pathophysiology of this disease, in which the exosomal content is related to mechanisms that will trigger its development. After platelet activation through ROS exposition, exosomes containing high concentrations of NADPH are released in heart blood vessels, those exosomes will be internalized in endothelial cells leading to cell death and cardiac dysfunction. On the opposite, exosomes derived from mesenchymal stem cells contain miR-223, that have anti-inflammatory properties, are released in less quantities in septic patients causing an imbalance that leads to cardiac dysfunction.

Current Status of Septic Cardiomyopathy: Basic Science and Clinical Progress

“…Exosomes are small cell-derived vesicles originate from leukocytes, platelets and dendritic cells, etc. (Monteiro et al, 2017). Exosomes are a double-edged sword that can protect and cause SCM.…”

“…Exosomes are a double-edged sword that can protect and cause SCM. The roles of exosomes in SCM is mainly considered from two mechanisms that are exosomal nicotinamide adenine dinucleotide phosphate (NADPH) and microRNA-223 (Monteiro et al, 2017). A study has shown that exosomes can induce vascular apoptosis and myocardial dysfunction by the mechanisms that are related to inflammation and oxidative stress (Real et al, 2018).…”

“…In addition, the attenuation of cardiac dysfunction and improvement of survival are noted in septic mice (Essandoh et al, 2015). Also, another component from exosomes, iNOS, can produce NO that is related to myocardial dysfunction in sepsis (Monteiro et al, 2017;Spiller et al, 2019). Figure 1 is the Illustration of the roles platelet-derived exosomes in SCM.…”

“…miR-223 can inhibit the expression of endothelial cell adhesion molecule (ICAM-1) and negatively regulates transcription activator 3 (STAT3). Studies have shown that miR-223 found in exosomes and derived from mesenchymal stem cells (MSC) has a protective effect on cardiac function (Monteiro et al, 2017;Ge, 2019). Less amounts of miR-223 from MSC-derived exosomes are observed in blood in patients with septic shock, suggesting an impact of exosomes on cardiac dysfunction and mortality (Monteiro et al, 2017).…”

“…Studies have shown that miR-223 found in exosomes and derived from mesenchymal stem cells (MSC) has a protective effect on cardiac function (Monteiro et al, 2017;Ge, 2019). Less amounts of miR-223 from MSC-derived exosomes are observed in blood in patients with septic shock, suggesting an impact of exosomes on cardiac dysfunction and mortality (Monteiro et al, 2017). Despite the inconsistencies regarding the role of exosomes in SCM, the association between SCM and exosomes has been established from current studies.…”