Plasma Exosomes and Improvements in Endothelial Function by Angiotensin 2 Type 1 Receptor or Cyclooxygenase 2 Blockade following Intermittent Hypoxia

Youssefnia, Nina; Foster, Glen E.; Beaudin, Andrew E.; Qiao, Zhuanhong; Pialoux, Vincent; Pun, Matiram; Hanly, Patrick J.; Kheirandish‐Gozal, Leila; Poulin, Marc J.; Gozal, David

doi:10.3389/fneur.2017.00709

Cited by 17 publications

(16 citation statements)

References 29 publications

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“…We and other have investigated cell uptake in several cell lines [ 150 , 151 , 152 , 153 ]. Several methods were used to study exosomal uptake in vitro and in vivo.…”

Section: Exosome Internalizationmentioning

confidence: 99%

“…Several methods were used to study exosomal uptake in vitro and in vivo. For examples, exosomes were labeled using different commercially available dyes including PKH26 Red and PKH67 Green Fluorescent Cell Linker Kit for General Cell Membrane Labeling [ 152 , 154 , 155 , 156 ]. Treatment of exosomes with proteinase K significantly reduced uptake by ovarian cancer cells.…”

Section: Exosome Internalizationmentioning

confidence: 99%

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Exosome and Macrophage Crosstalk in Sleep-Disordered Breathing-Induced Metabolic Dysfunction

Kheirandish‐Gozal

Gozal

2018

IJMS

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Obstructive sleep apnea (OSA) is a highly prevalent worldwide public health problem that is characterized by repetitive upper airway collapse leading to intermittent hypoxia, pronounced negative intrathoracic pressures, and recurrent arousals resulting in sleep fragmentation. Obesity is a major risk factor of OSA and both of these two closely intertwined conditions result in increased sympathetic activity, oxidative stress, and chronic low-grade inflammation, which ultimately contribute, among other morbidities, to metabolic dysfunction, as reflected by visceral white adipose tissue (VWAT) insulin resistance (IR). Circulating extracellular vesicles (EVs), including exosomes, are released by most cell types and their cargos vary greatly and reflect underlying changes in cellular homeostasis. Thus, exosomes can provide insights into how cells and systems cope with physiological perturbations by virtue of the identity and abundance of miRNAs, mRNAs, proteins, and lipids that are packaged in the EVs cargo, and are secreted from the cells into bodily fluids under normal as well as diseased states. Accordingly, exosomes represent a novel pathway via which a cohort of biomolecules can travel long distances and result in the modulation of gene expression in selected and targeted recipient cells. For example, exosomes secreted from macrophages play a critical role in innate immunity and also initiate the adaptive immune response within specific metabolic tissues such as VWAT. Under normal conditions, phagocyte-derived exosomes represent a large portion of circulating EVs in blood, and carry a protective signature against IR that is altered when secreting cells are exposed to altered physiological conditions such as those elicited by OSA, leading to emergence of IR within VWAT compartment. Consequently, increased understanding of exosome biogenesis and biology should lead to development of new diagnostic biomarker assays and personalized therapeutic approaches. Here, the evidence on the major biological functions of macrophages and exosomes as pathophysiological effectors of OSA-induced metabolic dysfunction is discussed.

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“…We and other have investigated cell uptake in several cell lines [ 150 , 151 , 152 , 153 ]. Several methods were used to study exosomal uptake in vitro and in vivo.…”

Section: Exosome Internalizationmentioning

confidence: 99%

Section: Exosome Internalizationmentioning

confidence: 99%

Exosome and Macrophage Crosstalk in Sleep-Disordered Breathing-Induced Metabolic Dysfunction

Kheirandish‐Gozal

Gozal

2018

IJMS

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“…Exosomes are a subtype of extracellular vesicles (EV) ranging from 50-200 nm in diameter, secreted by various cell types such as dendritic cells 1, macrophages 2, cancer cells 3-6 and mesenchymal stem cells 7. Exosomes have also been shown to be present in various physiological fluids 8-11. The combination of the inherent ability of exosomes to carry various biomolecules (e.g.…”

Section: Introductionmentioning

confidence: 99%

Membrane Radiolabelling of Exosomes for Comparative Biodistribution Analysis in Immunocompetent and Immunodeficient Mice - A Novel and Universal Approach

Faruqu¹,

Wang²,

Xu³

et al. 2019

Theranostics

110

109

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Extracellular vesicles, in particular exosomes, have recently gained interest as novel drug delivery vectors due to their biological origin and inherent intercellular biomolecule delivery capability. An in-depth knowledge of their in vivo biodistribution is therefore essential. This work aimed to develop a novel, reliable and universal method to radiolabel exosomes to study their in vivo biodistribution. Methods : Melanoma (B16F10) cells were cultured in bioreactor flasks to increase exosome yield. B16F10-derived exosomes (Exo B16 ) were isolated using ultracentrifugation onto a single sucrose cushion, and were characterised for size, yield, purity, exosomal markers and morphology using nanoparticle tracking analysis (NTA), protein measurements, flow cytometry and electron microscopy. Exo B16 were radiolabelled using 2 different approaches - intraluminal labelling (entrapment of 111 Indium via tropolone shuttling); and membrane labelling (chelation of 111 Indium via covalently attached bifunctional chelator DTPA-anhydride). Labelling efficiency and stability was assessed using gel filtration and thin layer chromatography. Melanoma-bearing immunocompetent (C57BL/6) and immunodeficient (NSG) mice were injected intravenously with radiolabelled Exo B16 (1x10 11 particles/mouse) followed by metabolic cages study, whole body SPECT-CT imaging and ex vivo gamma counting at 1, 4 and 24 h post-injection. Results : Membrane-labelled Exo B16 showed superior radiolabelling efficiency and radiochemical stability (19.2 ± 4.53 % and 80.4 ± 1.6 % respectively) compared to the intraluminal-labelled exosomes (4.73 ± 0.39 % and 14.21 ± 2.76 % respectively). Using the membrane-labelling approach, the in vivo biodistribution of Exo B16 in melanoma-bearing C57Bl/6 mice was carried out, and was found to accumulate primarily in the liver and spleen (~56% and ~38% ID/gT respectively), followed by the kidneys (~3% ID/gT). Exo B16 showed minimal tumour i.e. self-tissue accumulation (~0.7% ID/gT). The membrane-labelling approach was also used to study Exo B16 biodistribution in melanoma-bearing immunocompromised (NSG) mice, to compare with that in the immunocompetent C57Bl/6 mice. Similar biodistribution profile was observed in both C57BL/6 and NSG mice, where prominent accumulation was seen in liver and spleen, apart from the significantly lower tumour accumulation observed in the NSG mice (~0.3% ID/gT). Conclusion : Membrane radiolabelling of exosomes is a reliable approach that allows for accurate live imaging and quantitative biodistribution studies to be performed on potentially all exosome types wi...

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“…OSA has also been associated with the presence of systemic inflammation of as-yet unknown origin. This state may be influenced by epigenetic modifications induced by de-oxygenation/re-oxygenation phenomena, in which CIH is crucial [12,13]. Both morbid obesity (MO) and OSA patients have an increase in several factors associated with endothelial damage triggered by CIH [14].…”

Section: Introductionmentioning

confidence: 99%

Epigenetics dysfunction in morbid obesity with or without obstructive sleep apnoea: the EPIMOOSA study

et al. 2020

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Background: Obstructive sleep apnoea (OSA) and morbid obesity (MO), defined by a body mass index ≥35 kg/m 2 , are two closely related conditions. Recent studies suggest that circulating microRNA (miRNA) plays a potential role in the physiopathology of both conditions. To date, circulating miRNA expression has been studied separately in both conditions, but never jointly. The primary treatment of OSA is continuous positive airway pressure (CPAP), whereas bariatric surgery (BS) is the treatment of choice for MO. We have thus initiated the Epigenetics modification in Morbid Obesity and Obstructive Sleep Apnoea (EPIMOOSA) study (ClinicalTrials.gov identifier: NCT03995836). Methods/design: EPIMOOSA is a prospective non-interventional cohort study aiming to recruit 45 MO patients who are candidates for BS. Three groups will be formed: MO without OSA, MO with OSA without CPAP and MO with OSA and CPAP. All of them will be followed up in 4 visits: baseline, 6 months prior to BS and 3, 6 and 12 months post-BS. At baseline, OSA status will be assessed by home sleep polygraphy (HSP), and CPAP will be adopted according to national guidelines. A specific standardized questionnaire (including medical conditions and AOS-related symptoms) and anthropometrical examination will be performed at each visit. Blood samples will be obtained at each visit for immediate standard biochemistry, haematology and inflammatory cytokines. For biobanking, serum, plasma, and circulating exosomes will also be obtained. Twenty-four hours of blood pressure and electrocardiogram (ECG) Holter monitoring will be performed at all visits. A new HSP will be performed at the last visit. Finally, the three groups will be sex-and age-matched with participants in the EPIOSA study, an ongoing study aimed at understanding epigenetic changes in non-obese OSA patients. Discussion: EPIMOOSA will evaluate changes in circulating miRNA in MO with or without OSA for the first time. In addition, EPIMOOSA will be able to elucidate the influence of OSA in MO patients and how specific and combined treatments alter miRNA expression.

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Plasma Exosomes and Improvements in Endothelial Function by Angiotensin 2 Type 1 Receptor or Cyclooxygenase 2 Blockade following Intermittent Hypoxia

Cited by 17 publications

References 29 publications

Exosome and Macrophage Crosstalk in Sleep-Disordered Breathing-Induced Metabolic Dysfunction

Exosome and Macrophage Crosstalk in Sleep-Disordered Breathing-Induced Metabolic Dysfunction

Membrane Radiolabelling of Exosomes for Comparative Biodistribution Analysis in Immunocompetent and Immunodeficient Mice - A Novel and Universal Approach

Epigenetics dysfunction in morbid obesity with or without obstructive sleep apnoea: the EPIMOOSA study

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