The Role of Lipopolysaccharide-Induced Extracellular Vesicles in Cardiac Cell Death.

Courtnee’ R Bell,Glenn C Rowe,Leandra B Jones,Gulnaz T Javan,Brian Sims,Brennetta J Crenshaw,Sanjay Kumar,Qiana L Matthews

doi:10.3390/biology8040069

Courtnee’ R Bell, Glenn C Rowe + Show 6 more

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https://doi.org/10.3390/biology8040069

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Abstract

Exosomes play a crucial role in the progression of infectious diseases, as exosome release and biogenesis are affected by external factors, such as pathogenic infections. Pyrogens may aide in the progression of diseases by triggering inflammation, endothelial cell injury, and arterial plaque rupture, all of which can lead to acute coronary disease, resulting in cardiac tissue death and the onset of a cardiac event (CE). To better understand the effects of Gram-negative bacterial infections on exosome composition and biogenesis, we examined exosome characteristics after treatment of AC16 human cardiomyocytes with lipopolysaccharide (LPS), which served as a model system for Gram-negative bacterial infection. Using increasing doses (0, 0.1, 1, or 10 µg) of LPS, we showed that treatment with LPS substantially altered the composition of AC16-derived exosomes. Both the relative size and the quantity (particles/mL) of exosomes were decreased significantly at all tested concentrations of LPS treatment compared to the untreated group. In addition, LPS administration reduced the expression of exosomal proteins that are related to exosomal biogenesis. Conversely, we observed an increase in immunomodulators present after LPS administration. This evaluation of the impact of LPS on cardiac cell death and exosome composition will yield new insight into the importance of exosomes in a variety of physiological and pathological processes as it relates to disease progression, diagnosis, and treatment.

Highlights

Gram-negative bacteria are responsible for millions of nosocomial infections and are of particular interest [1]
To examine the effect of LPS treatment on human cardiomyocytes, AC16 cells were treated with increasing concentrations of LPS, which represent varying levels of bacterial infection [18,19,20]
With an increase in antibiotic resistance in opportunistic bacteria that can invade the a pressing need to understand the role of Gram-negative bacteria in cardiac cell death to inform the heart,Gram-negative and a concomitant decrease in new effective drugs to for treatmillions these bacterial infections, is a bacterial infections are responsible of infections andthere deaths development of novel treatment strategies

Summary

Introduction

Gram-negative bacteria are responsible for millions of nosocomial infections and are of particular interest [1]. These microorganisms are highly efficient at transferring essential genes via quorum sensing, allowing these pathogens to develop mechanisms related to resistance and virulence to further encourage the propagation of the bacteria [2,3,4]. Most Gram-negative bacteria possess lipopolysaccharide (LPS), an endotoxin that is present in the outer leaflet of the outer membrane of the Biology 2019, 8, 69; doi:10.3390/biology8040069 www.mdpi.com/journal/biology. The precise molecular structure of LPS differs from one bacterium to another, most enzymes and genes related to LPS formulation and transportation were identified in Escherichia coli

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