Enrichment of the erythrocyte miR-451a in brain extracellular vesicles following impairment of the blood-brain barrier

Koopaei, Nasser Nassiri; Chowdhury, Ekram Ahmed; Jiang, Jinmai; Noorani, Behnam; Silva, Lais Da; Bulut, Gamze B.; Hakimjavadi, Hesamedin; Chamala, Srikar; Bickel, Ulrich; Schmittgen, Thomas D.

doi:10.1016/j.neulet.2021.135829

Cited by 13 publications

(8 citation statements)

References 33 publications

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“…we found hsa-miR-320e and hsa-miR-451a that had already been described as potential biomarkers for early diagnosis of acute stroke (Stylli et al, 2017;Koopaei et al, 2021;Aldous et al, 2022) and hsa-miR-630 that had also been related with cancer disease (Wu et al, 2018;Liu et al, 2021) and SAH (Wang et al, 2014;Sun et al, 2019). Therefore, after an acute brain injury such as SAH, there seems to be an increased expression of specific miRNAs which might activate or inhibit signaling pathways responsible of DCI and clinical outcomes.…”

Section: Micrornas Are Overexpressed In the Cerebrospinal Fluid After...mentioning

confidence: 62%

MicroRNA cerebrospinal fluid profile during the early brain injury period as a biomarker in subarachnoid hemorrhage patients

Pedrosa

Hoyos

Reyes

et al. 2022

Front. Cell. Neurosci.

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IntroductionDelayed cerebral ischemia (DCI) is a dreadful complication present in up to 30% of patients with spontaneous subarachnoid hemorrhage (SAH). Indeed, DCI is one of the main causes of long-term disability in SAH, yet its prediction and prevention are troublesome in poor-grade SAH cases. In this prospective study, we explored the potential role of micro ribonucleic acid (microRNA, abbreviated miRNAs)—small non-coding RNAs involved in clue gene regulation at the post-transcriptional level—as biomarkers of neurological outcomes in SAH patients.MethodsWe analyzed the expression of several miRNAs present in the cerebrospinal fluid (CSF) of SAH patients during the early stage of the disease (third-day post-hemorrhage). NanoString Technologies were used for the characterization of the CSF samples.ResultsWe found an overexpression of miRNAs in the acute stage of 57 SAH in comparison with 10 non-SAH controls. Moreover, a differential expression of specific miRNAs was detected according to the severity of clinical onset, but also regarding the development of DCI and the midterm functional outcomes.ConclusionThese observations reinforce the potential utility of miRNAs as prognostic and diagnostic biomarkers in SAH patients. In addition, the identification of specific miRNAs related to SAH evolution might provide insights into their regulatory functions of pathophysiological pathways, such as the TGF-β inflammatory pathway and blood-brain barrier disruption.

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Section: Micrornas Are Overexpressed In the Cerebrospinal Fluid After...mentioning

confidence: 62%

MicroRNA cerebrospinal fluid profile during the early brain injury period as a biomarker in subarachnoid hemorrhage patients

Pedrosa

Hoyos

Reyes

et al. 2022

Front. Cell. Neurosci.

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“…Systemic intravenous injection of the hyperosmolar agent mannitol is used clinically to reduce cerebral edema in acute conditions [38]. In contrast, at a high concentration (25% w/v), bolus intra-arterial injection of mannitol results in endothelial cell shrinkage, leading to a transient opening of the BBB [39][40][41]. Hyperosmolar BBB opening has been used in clinical and translational settings to facilitate the delivery of chemotherapeutics, stem cells, and viral vectors into the brain [40,42,43].…”

Section: Discussionmentioning

confidence: 99%

A Quasi-Physiological Microfluidic Blood-Brain Barrier Model for Brain Permeability Studies

et al. 2021

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Microfluidics-based organ-on-a-chip technology allows for developing a new class of in-vitro blood-brain barrier (BBB) models that recapitulate many hemodynamic and architectural features of the brain microvasculature not attainable with conventional two-dimensional platforms. Herein, we describe and validate a novel microfluidic BBB model that closely mimics the one in situ. Induced pluripotent stem cell (iPSC)-derived brain microvascular endothelial cells (BMECs) were juxtaposed with primary human pericytes and astrocytes in a co-culture to enable BBB-specific characteristics, such as low paracellular permeability, efflux activity, and osmotic responses. The permeability coefficients of [13C12] sucrose and [13C6] mannitol were assessed using a highly sensitive LC-MS/MS procedure. The resulting BBB displayed continuous tight-junction patterns, low permeability to mannitol and sucrose, and quasi-physiological responses to hyperosmolar opening and p-glycoprotein inhibitor treatment, as demonstrated by decreased BBB integrity and increased permeability of rhodamine 123, respectively. Astrocytes and pericytes on the abluminal side of the vascular channel provided the environmental cues necessary to form a tight barrier and extend the model’s long-term viability for time-course studies. In conclusion, our novel multi-culture microfluidic platform showcased the ability to replicate a quasi-physiological brain microvascular, thus enabling the development of a highly predictive and translationally relevant BBB model.

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“…54,55 In cardiovascular and metabolic diseases, the amounts of miRNAs harbored by RBCs are altered. 9,19,22,23 It is proposed that miRNAs are dysregulated by different factors during RBC development. The amounts of miRNAs in RBCs can also be affected by alteration of the uptake of circulating miRNA.…”

Section: Rbcs As Microrna Poolmentioning

confidence: 99%

“…18 Several studies have shown that RBC-derived miRNAs can reflect the miRNAs patterns in whole blood, serum, or plasma, 9,19–21 and the expression levels of miRNAs in RBCs are changed in cardiovascular and metabolic pathology. 9,19,22,23 However, the mechanism by which miRNAs function in the RBCs and the implications of altered RBC-derived miRNAs regulating cardiovascular (dys)function remain unclear.…”

mentioning

confidence: 99%

Erythrocyte-Derived microRNAs: Emerging Players in Cardiovascular and Metabolic Disease

Kontidou

Collado

Pernow

et al. 2023

ATVB

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Recent studies have demonstrated a novel function of red blood cells (RBCs) beyond their classical role as gas transporters, that is, RBCs undergo functional alterations in cardiovascular and metabolic disease, and RBC dysfunction is associated with hypertension and the development of cardiovascular injury in type 2 diabetes, heart failure, preeclampsia, familial hypercholesterolemia/dyslipidemia, and COVID-19. The underlying mechanisms include decreased nitric oxide bioavailability, increased arginase activity, and reactive oxygen species formation. Of interest, RBCs contain diverse and abundant micro (mi)RNAs. microRNA expression pattern in RBCs reflects the expression in the whole blood, serum, and plasma. microRNA levels in RBCs have been found to be altered in various cardiovascular and metabolic diseases, which contributes to the development of cardiovascular complications. Evidence has shown that RBC-derived miRNAs interact with the cardiovascular system via extracellular vesicles and argonaute RISC catalytic component 2 as carriers. Alteration of RBC-to-vascular communication via miRNAs may serve as potential disease mechanism for vascular complications. The present review summarizes RBCs and their released miRNAs as potential mediators of cardiovascular injury. We further focus on the possible mechanisms by which RBC-derived miRNAs regulate cardiovascular function. A better understanding of the function of RBC-derived miRNAs will increase insights into the disease mechanism and potential targets for the treatment of cardiovascular complications.

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Enrichment of the erythrocyte miR-451a in brain extracellular vesicles following impairment of the blood-brain barrier

Cited by 13 publications

References 33 publications

MicroRNA cerebrospinal fluid profile during the early brain injury period as a biomarker in subarachnoid hemorrhage patients

MicroRNA cerebrospinal fluid profile during the early brain injury period as a biomarker in subarachnoid hemorrhage patients

A Quasi-Physiological Microfluidic Blood-Brain Barrier Model for Brain Permeability Studies

Erythrocyte-Derived microRNAs: Emerging Players in Cardiovascular and Metabolic Disease

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