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

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.

Effects of Cocaine on Human Glial-Derived Extracellular Vesicles

“…We found that cocaine exposure did not alter the expression of cleaved caspase-9 or -3 ( Figures 3B,C and Supplementary Figures 3B,C ). However, 100 μM cocaine significantly increased histone H2A.x expression ( Figure 3D and Supplementary Figure 3D ), supporting previous findings ( Bell et al, 2019 ).…”

“…The size and quantity of isolated EVs were measured using NTA and TEM. We found that cocaine did not alter the size of EVs and EVs are visible and easily recognizable ( Figure 1B and Supplementary Figures 1B,D–F ), which ranged from 30 to 150 nm in diameter across conditions, consistent with previous studies ( Bell et al, 2019 ; Crenshaw et al, 2019 ; Jones et al, 2019 ; Kumar et al, 2020 ). However, 100 μM cocaine slightly reduced the number of EV particles per mL compared with the 1 μM cocaine and control conditions, although this difference was not significant ( Figure 1C and Supplementary Figures 1C,D–F ).…”

“…Medium only was used as a control. After incubating cells with cocaine, EVs released into the medium were isolated and purified using a standard ultracentrifugation procedure ( Bell et al, 2019 ; Crenshaw et al, 2019 ; Jones et al, 2019 ). The size and quantity of isolated EVs were measured using NTA and TEM.…”

Lipopolysaccharide administration alters extracellular vesicles in human lung-cancer cells and mice

“…After 24 hrs, cells were washed and media was replaced with exosome-depleted media. The experimental flasks were treated with 0.1 μg/mL, 1 μg/mL or 10 μg/mL of LPS for 48 hrs [11]. Following treatment, cell morphology and integrity were visualized and media was collected.…”

PD-1 inhibitor inducing exosomal miR-34a-5p expression mediates the cross talk between cardiomyocyte and macrophage in immune checkpoint inhibitor–related cardiac dysfunction

“…14 The recent literature suggests that condition-modified exosomes induce cardiac injury. 15 Macrophage-derived exosomes in patients with diabetes showed proinflammation function, leading to cardiac fibrosis. 16 Meanwhile, exosomes derived from modified macrophages showed a pro-DNA damaging effect, thus leading to senescence.…”