Plasma exosomes in OSA patients promote endothelial senescence: effect of long-term adherent continuous positive airway pressure

Khalyfa, Abdelnaby; Marı́n, José Marı́a; Qiao, Zhuanhong; Sanz-Rubio, David; Kheirandish‐Gozal, Leila; Gozal, David

doi:10.1093/sleep/zsz217

Cited by 34 publications

(27 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, we revealed the tendency that SIRT1 was decreased in DR patients' plasma using the ELISA method (Supplementary Figure 1). Mariani et al (2015Mariani et al ( , 2016 and Khalyfa et al (2019) reported that SIRT1 was downregulated in DM-associated metabolic diseases plasma and the decreased exosome SIRT1 might be correlated with endothelial dysfunction. However, the regulatory mechanism of diabetes to SIRT1 is not clear.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-29b-3p Promotes Human Retinal Microvascular Endothelial Cell Apoptosis via Blocking SIRT1 in Diabetic Retinopathy

Yong

Cui²,

Liu³

et al. 2020

Front. Physiol.

View full text Add to dashboard Cite

Background: Diabetic retinopathy (DR) is a main complication of diabetes mellitus (DM). Recent studies have implicated microRNAs in human retinal microvascular endothelial cell (HRMEC) dysfunction. In this study, we aim to investigate the apoptotic promotion of miR-29b-3p by blocking SIRT1 in HRMEC for DR situation. Method: Blood samples were obtained from DR patients and controls. Dual-luciferase reporter assay using HEK-293T cells was performed to show the direct interaction of miR-29b-3p and the 3 UTR of SIRT1. HRMECs were exposed to 5.5 mmol/L of glucose (normal control), 5.5 mmol/L of glucose and 24.5 mmol/L of mannitol (osmotic pressure control), 30 mmol/L of glucose [hyperglycemia (HG)], 150 µmol/L of CoCl 2 (hypoxia), and 30 mmol/L of glucose plus 150 µmol/L of CoCl 2 (HG-CoCl 2). To identify the regulating relationship between miR-29b-3p and SIRT1, HRMECs were transfected with miR-29b-3p mimics/inhibitors or their negative controls. SRT1720 was used as a SIRT1 agonist. Cell viability was assessed with the cell counting kit-8 (CCK-8) assay, and apoptotic cells were stained by one-step terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay kit. Gene and protein expression were assayed by quantitative real-time reverse transcriptase-PCR (RT-qPCR) and western blotting separately. Result: MiR-29b-3p was upregulated to 3.2-fold, and SIRT1 protein was downregulated to 65% in DR patients. Dual-luciferase reporter assay showed the direct interaction of miR-29b-3p and SIRT1. HRMECs were identified as >95% positive for CD31 and von Willebrand factor (vWF). MiR-29b-3p and Bax/Bcl-2 ratio was upregulated, whereas SIRT1 was downregulated in HRMECs in the HG-CoCl 2 condition. Decreased cell viability and upregulated apoptosis were also found in HRMECs of the HG-CoCl 2 condition. Upregulated miR-29b-3p decreased the expression of SIRT1 and increased the ratio of Bax/Bcl-2, whereas downregulated miR-29b-3p increased the expression of SIRT1 protein and downregulated the ratio of

show abstract

Section: Discussionmentioning

confidence: 99%

MicroRNA-29b-3p Promotes Human Retinal Microvascular Endothelial Cell Apoptosis via Blocking SIRT1 in Diabetic Retinopathy

Yong

Cui²,

Liu³

et al. 2020

Front. Physiol.

View full text Add to dashboard Cite

show abstract

“…EVs released from parental cells may interact with target cells, leading to the subsequent influence of target cell behavior and phenotype features [ 109 ]. In plasma, we have isolated EVs from adult, children, and animals exposed to sleep apnea [ 107 , 110 , 111 , 112 , 113 , 114 , 115 ].…”

Section: Red Blood Cells Extracellular Vesiclementioning

confidence: 99%

“…The most common methods for isolation of EVs or exosomes can be applied from one source to another with some modification. The following are the most common methods used for isolating EVs: ultracentrifugation, sequential centrifugation, density gradient, filtration, sucrose gradient precipitation, polyethylene glycol, acetate, size-exclusion column (Sepharose gel, Sephadex affinity-based capture), and magnetic beads [ 110 , 111 , 112 , 113 , 125 , 126 , 127 , 128 ]. Each of these methods has advantages and disadvantages which include time-consuming, labor-intensive, and expensive equipment.…”

Section: Red Blood Cells Extracellular Vesiclementioning

confidence: 99%

“…As a result, parental cells can communicate with specific proximal or distal target cells through exosome amplification. Recent studies have shown a wide range of multiple functions of these vesicles in several biological processes including antigen presentation, neuronal communication, blood coagulation, wound healing, and senescent [ 107 , 110 , 233 , 234 , 235 ]. EVs are also playing an important role in pathogenic processes including cancer, autoimmune diseases, inflammation, infection, and metabolic and cardiovascular diseases [ 108 , 236 , 237 ].…”

Section: Extracellular Vesicles Internalizationmentioning

confidence: 99%

See 1 more Smart Citation

The Mystery of Red Blood Cells Extracellular Vesicles in Sleep Apnea with Metabolic Dysfunction

Sanz-Rubio

2021

IJMS

Self Cite

View full text Add to dashboard Cite

Sleep is very important for overall health and quality of life, while sleep disorder has been associated with several human diseases, namely cardiovascular, metabolic, cognitive, and cancer-related alterations. Obstructive sleep apnea (OSA) is the most common respiratory sleep-disordered breathing, which is caused by the recurrent collapse of the upper airway during sleep. OSA has emerged as a major public health problem and increasing evidence suggests that untreated OSA can lead to the development of various diseases including neurodegenerative diseases. In addition, OSA may lead to decreased blood oxygenation and fragmentation of the sleep cycle. The formation of free radicals or reactive oxygen species (ROS) can emerge and react with nitric oxide (NO) to produce peroxynitrite, thereby diminishing the bioavailability of NO. Hypoxia, the hallmark of OSA, refers to a decline of tissue oxygen saturation and affects several types of cells, playing cell-to-cell communication a vital role in the outcome of this interplay. Red blood cells (RBCs) are considered transporters of oxygen and nutrients to the tissues, and these RBCs are important interorgan communication systems with additional functions, including participation in the control of systemic NO metabolism, redox regulation, blood rheology, and viscosity. RBCs have been shown to induce endothelial dysfunction and increase cardiac injury. The mechanistic links between changes of RBC functional properties and cardiovascular are largely unknown. Extracellular vesicles (EVs) are secreted by most cell types and released in biological fluids both under physiological and pathological conditions. EVs are involved in intercellular communication by transferring complex cargoes including proteins, lipids, and nucleic acids from donor cells to recipient cells. Advancing our knowledge about mechanisms of RBC-EVs formation and their pathophysiological relevance may help to shed light on circulating EVs and to translate their application to clinical practice. We will focus on the potential use of RBC-EVs as valuable diagnostic and prognostic biomarkers and state-specific cargoes, and possibilities as therapeutic vehicles for drug and gene delivery. The use of RBC-EVs as a precision medicine for the diagnosis and treatment of the patient with sleep disorder will improve the prognosis and the quality of life in patients with cardiovascular disease (CVD).

show abstract

“…Exosomes, a class of extracellular vesicles, are very small vesicles ranging in size from 30 to 120 nm. These vesicles are generated by many, if not all, cells in the body, and can perhaps be detected in all biological fluids [27,[31][32][33][34][35], where they participate in a vast array of physiological processes, and more specifically, mediate critical aspects of intercellular communication [36] through delivery of their functional cargo [31,34,[37][38][39][40].…”

Section: Introductionmentioning

confidence: 99%

Plasma Extracellular Vesicles in Children with OSA Disrupt Blood–Brain Barrier Integrity and Endothelial Cell Wound Healing In Vitro

Gozal

Kheirandish‐Gozal

2019

IJMS

Self Cite

View full text Add to dashboard Cite

Pediatric obstructive sleep apnea (P-OSA) is associated with neurocognitive deficits and endothelial dysfunction, suggesting the possibility that disruption of the blood–brain barrier (BBB) may underlie these morbidities. Extracellular vesicles (EVs), which include exosomes, are small particles involved in cell–cell communications via different mechanisms and could play a role in OSA-associated end-organ injury. To examine the roles of EVs in BBB dysfunction, we recruited three groups of children: (a) absence of OSA or cognitive deficits (CL, n = 6), (b) OSA but no evidence of cognitive deficits (OSA-NC(−), n = 12), and (c) OSA with evidence of neurocognitive deficits (OSA-NC(+), n = 12). All children were age-, gender-, ethnicity-, and BMI-z-score-matched, and those with OSA were also apnea–hypopnea index (AHI)-matched. Plasma EVs were characterized, quantified, and applied on multiple endothelial cell types (HCAEC, HIAEC, human HMVEC-D, HMVEC-C, HMVEC-L, and hCMEC/D3) while measuring monolayer barrier integrity and wound-healing responses. EVs from OSA children induced significant declines in hCMEC/D3 transendothelial impedance compared to CL (p < 0.001), and such changes were greater in NC(+) compared to NC(−) (p < 0.01). The effects of EVs from each group on wound healing for HCAEC, HIAEC, HMVED-d, and hCMEC/D3 cells were similar, but exhibited significant differences across the three groups, with evidence of disrupted wound healing in P-OSA. However, wound healing in HMVEC-C was only affected by NC(+) (p < 0.01 vs. NC(−) or controls (CO). Furthermore, no significant differences emerged in HMVEC-L cell wound healing across all three groups. We conclude that circulating plasma EVs in P-OSA disrupt the integrity of the BBB and exert adverse effects on endothelial wound healing, particularly among OSA-NC(+) children, while also exhibiting endothelial cell type selectivity. Thus, circulating EVs cargo may play important roles in the emergence of end-organ morbidity in pediatric OSA.

show abstract

Plasma exosomes in OSA patients promote endothelial senescence: effect of long-term adherent continuous positive airway pressure

Cited by 34 publications

References 77 publications

MicroRNA-29b-3p Promotes Human Retinal Microvascular Endothelial Cell Apoptosis via Blocking SIRT1 in Diabetic Retinopathy

MicroRNA-29b-3p Promotes Human Retinal Microvascular Endothelial Cell Apoptosis via Blocking SIRT1 in Diabetic Retinopathy

The Mystery of Red Blood Cells Extracellular Vesicles in Sleep Apnea with Metabolic Dysfunction

Plasma Extracellular Vesicles in Children with OSA Disrupt Blood–Brain Barrier Integrity and Endothelial Cell Wound Healing In Vitro

Contact Info

Product

Resources

About