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Tytuł pozycji:

Increased Catecholamine Levels and Inflammatory Mediators Alter Barrier Properties of Brain Microvascular Endothelial Cells in vitro .

Tytuł:
Increased Catecholamine Levels and Inflammatory Mediators Alter Barrier Properties of Brain Microvascular Endothelial Cells in vitro .
Autorzy:
Ittner C; Department of Anaesthesia and Critical Care, University of Würzburg, Würzburg, Germany.
Burek M; Department of Anaesthesia and Critical Care, University of Würzburg, Würzburg, Germany.
Störk S; Comprehensive Heart Failure Center, University of Würzburg, Würzburg, Germany.
Nagai M; Department of Internal Medicine, General Medicine and Cardiology, Hiroshima City Asa Hospital, Hiroshima, Japan.
Förster CY; Department of Anaesthesia and Critical Care, University of Würzburg, Würzburg, Germany.
Źródło:
Frontiers in cardiovascular medicine [Front Cardiovasc Med] 2020 May 05; Vol. 7, pp. 73. Date of Electronic Publication: 2020 May 05 (Print Publication: 2020).
Typ publikacji:
Journal Article
Język:
English
Imprint Name(s):
Original Publication: Lausanne : Frontiers Media S.A., [2014]-
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Contributed Indexing:
Keywords: blood-brain barrier; cEND cell line; catecholamines; in vitro; inflammation; microvascular endothelium; takotsubo syndrome
Entry Date(s):
Date Created: 20200521 Latest Revision: 20200928
Update Code:
20240105
PubMed Central ID:
PMC7214675
DOI:
10.3389/fcvm.2020.00073
PMID:
32432126
Czasopismo naukowe
Recent studies have suggested a pathogenetic link between ischemic stroke and Takotsubo cardiomyopathy (TCM) with poor outcome, when occurring simultaneously. Increased catecholamine (CAT) levels as well as elevated inflammatory mediators (INF) are found in the blood of patients with ischemic stroke concomitant with Takotsubo syndrome (TTS). On molecular level, the impact of these stressors combined with hypoxemia could compromise the integrity of the blood brain barrier (BBB) resulting in poor outcomes. As a first step in the direction of investigating possible molecular mechanisms, an in vitro model of the described pathological constellation was designed. An immortalized murine microvascular endothelial cell line from the cerebral cortex (cEND) was used as an established in vitro model of the BBB. cEND cells were treated with supraphysiological concentrations of CAT (dopamine, norepinephrine, epinephrine) and INF (TNF-α and Interleukin-6). Simultaneously, cells were exposed to oxygen glucose deprivation (OGD) as an established in vitro model of ischemic stroke with/without subsequent reoxygenation. We investigated the impact on cell morphology and cell number by immunofluorescence staining. Furthermore, alterations of selected tight and adherens junction proteins forming paracellular barrier as well as integrins mediating cell-matrix adhesion were determined by RT-PCR and/or Western Blot technique. Especially by choosing this wide range of targets, we give a detailed overview of molecular changes leading to compromised barrier properties. Our data show that the proteins forming the BBB and the cell count are clearly influenced by CAT and INF applied under OGD conditions. Most of the investigated proteins are downregulated, so a negative impact on barrier integrity can be assumed. The structures affected by treatment with CAT and INF are potential targets for future therapies in ischemic stroke and TTS.
(Copyright © 2020 Ittner, Burek, Störk, Nagai and Förster.)

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