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Endothelial-derived extracellular vesicles induce cerebrovascular dysfunction in inflammation

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Endothelial-derived extracellular vesicles induce cerebrovascular dysfunction in inflammation. / Roig-Carles, D.; Willms, E.; Fontijn, R.D.; Martinez-Pacheco, S.; Mäger, I.; de Vries, H.E.; Hirst, M.; Sharrack, B.; Male, D.K.; Hawkes, C.A.; Romero, I.A.

In: Pharmaceutics, Vol. 13, No. 9, 1525, 21.09.2021.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Harvard

Roig-Carles, D, Willms, E, Fontijn, RD, Martinez-Pacheco, S, Mäger, I, de Vries, HE, Hirst, M, Sharrack, B, Male, DK, Hawkes, CA & Romero, IA 2021, 'Endothelial-derived extracellular vesicles induce cerebrovascular dysfunction in inflammation', Pharmaceutics, vol. 13, no. 9, 1525. https://doi.org/10.3390/pharmaceutics13091525

APA

Roig-Carles, D., Willms, E., Fontijn, R. D., Martinez-Pacheco, S., Mäger, I., de Vries, H. E., Hirst, M., Sharrack, B., Male, D. K., Hawkes, C. A., & Romero, I. A. (2021). Endothelial-derived extracellular vesicles induce cerebrovascular dysfunction in inflammation. Pharmaceutics, 13(9), [1525]. https://doi.org/10.3390/pharmaceutics13091525

Vancouver

Roig-Carles D, Willms E, Fontijn RD, Martinez-Pacheco S, Mäger I, de Vries HE et al. Endothelial-derived extracellular vesicles induce cerebrovascular dysfunction in inflammation. Pharmaceutics. 2021 Sep 21;13(9). 1525. https://doi.org/10.3390/pharmaceutics13091525

Author

Roig-Carles, D. ; Willms, E. ; Fontijn, R.D. ; Martinez-Pacheco, S. ; Mäger, I. ; de Vries, H.E. ; Hirst, M. ; Sharrack, B. ; Male, D.K. ; Hawkes, C.A. ; Romero, I.A. / Endothelial-derived extracellular vesicles induce cerebrovascular dysfunction in inflammation. In: Pharmaceutics. 2021 ; Vol. 13, No. 9.

Bibtex

@article{51fe1a540e444e6284f23a8ee5ce236d,
title = "Endothelial-derived extracellular vesicles induce cerebrovascular dysfunction in inflammation",
abstract = "Blood–brain barrier (BBB) dysfunction is a key hallmark in the pathology of many neu-roinflammatory disorders. Extracellular vesicles (EVs) are lipid membrane-enclosed carriers of molecular cargo that are involved in cell-to-cell communication. Circulating endothelial EVs are increased in the plasma of patients with neurological disorders, and immune cell-derived EVs are known to modulate cerebrovascular functions. However, little is known about whether brain endothelial cell (BEC)-derived EVs themselves contribute to BBB dysfunction. Human cerebral micro-vascular cells (hCMEC/D3) were treated with TNFα and IFNy, and the EVs were isolated and char-acterised. The effect of EVs on BBB transendothelial resistance (TEER) and leukocyte adhesion in hCMEC/D3 cells was measured by electric substrate cell-substrate impedance sensing and the flow-based T-cell adhesion assay. EV-induced molecular changes in recipient hCMEC/D3 cells were an-alysed by RT-qPCR and Western blotting. A stimulation of na{\"i}ve hCMEC/D3 cells with small EVs (sEVs) reduced the TEER and increased the shear-resistant T-cell adhesion. The levels of microRNA-155, VCAM1 and ICAM1 were increased in sEV-treated hCMEC/D3 cells. Blocking the expression of VCAM1, but not of ICAM1, prevented sEV-mediated T-cell adhesion to brain endothelia. These results suggest that sEVs derived from inflamed BECs promote cerebrovascular dysfunction. These findings may provide new insights into the mechanisms involving neuroinflammatory disorders. ",
keywords = "Blood–brain barrier, Cell-to-cell communication, Exosomes, Extracellular vesicles, Neuroinflammation",
author = "D. Roig-Carles and E. Willms and R.D. Fontijn and S. Martinez-Pacheco and I. M{\"a}ger and {de Vries}, H.E. and M. Hirst and B. Sharrack and D.K. Male and C.A. Hawkes and I.A. Romero",
year = "2021",
month = sep,
day = "21",
doi = "10.3390/pharmaceutics13091525",
language = "English",
volume = "13",
journal = "Pharmaceutics",
issn = "1999-4923",
publisher = "MDPI AG",
number = "9",

}

RIS

TY - JOUR

T1 - Endothelial-derived extracellular vesicles induce cerebrovascular dysfunction in inflammation

AU - Roig-Carles, D.

AU - Willms, E.

AU - Fontijn, R.D.

AU - Martinez-Pacheco, S.

AU - Mäger, I.

AU - de Vries, H.E.

AU - Hirst, M.

AU - Sharrack, B.

AU - Male, D.K.

AU - Hawkes, C.A.

AU - Romero, I.A.

PY - 2021/9/21

Y1 - 2021/9/21

N2 - Blood–brain barrier (BBB) dysfunction is a key hallmark in the pathology of many neu-roinflammatory disorders. Extracellular vesicles (EVs) are lipid membrane-enclosed carriers of molecular cargo that are involved in cell-to-cell communication. Circulating endothelial EVs are increased in the plasma of patients with neurological disorders, and immune cell-derived EVs are known to modulate cerebrovascular functions. However, little is known about whether brain endothelial cell (BEC)-derived EVs themselves contribute to BBB dysfunction. Human cerebral micro-vascular cells (hCMEC/D3) were treated with TNFα and IFNy, and the EVs were isolated and char-acterised. The effect of EVs on BBB transendothelial resistance (TEER) and leukocyte adhesion in hCMEC/D3 cells was measured by electric substrate cell-substrate impedance sensing and the flow-based T-cell adhesion assay. EV-induced molecular changes in recipient hCMEC/D3 cells were an-alysed by RT-qPCR and Western blotting. A stimulation of naïve hCMEC/D3 cells with small EVs (sEVs) reduced the TEER and increased the shear-resistant T-cell adhesion. The levels of microRNA-155, VCAM1 and ICAM1 were increased in sEV-treated hCMEC/D3 cells. Blocking the expression of VCAM1, but not of ICAM1, prevented sEV-mediated T-cell adhesion to brain endothelia. These results suggest that sEVs derived from inflamed BECs promote cerebrovascular dysfunction. These findings may provide new insights into the mechanisms involving neuroinflammatory disorders.

AB - Blood–brain barrier (BBB) dysfunction is a key hallmark in the pathology of many neu-roinflammatory disorders. Extracellular vesicles (EVs) are lipid membrane-enclosed carriers of molecular cargo that are involved in cell-to-cell communication. Circulating endothelial EVs are increased in the plasma of patients with neurological disorders, and immune cell-derived EVs are known to modulate cerebrovascular functions. However, little is known about whether brain endothelial cell (BEC)-derived EVs themselves contribute to BBB dysfunction. Human cerebral micro-vascular cells (hCMEC/D3) were treated with TNFα and IFNy, and the EVs were isolated and char-acterised. The effect of EVs on BBB transendothelial resistance (TEER) and leukocyte adhesion in hCMEC/D3 cells was measured by electric substrate cell-substrate impedance sensing and the flow-based T-cell adhesion assay. EV-induced molecular changes in recipient hCMEC/D3 cells were an-alysed by RT-qPCR and Western blotting. A stimulation of naïve hCMEC/D3 cells with small EVs (sEVs) reduced the TEER and increased the shear-resistant T-cell adhesion. The levels of microRNA-155, VCAM1 and ICAM1 were increased in sEV-treated hCMEC/D3 cells. Blocking the expression of VCAM1, but not of ICAM1, prevented sEV-mediated T-cell adhesion to brain endothelia. These results suggest that sEVs derived from inflamed BECs promote cerebrovascular dysfunction. These findings may provide new insights into the mechanisms involving neuroinflammatory disorders.

KW - Blood–brain barrier

KW - Cell-to-cell communication

KW - Exosomes

KW - Extracellular vesicles

KW - Neuroinflammation

U2 - 10.3390/pharmaceutics13091525

DO - 10.3390/pharmaceutics13091525

M3 - Journal article

VL - 13

JO - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 9

M1 - 1525

ER -