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19.01.2017 | Original Article

MiR-126 Affects Brain-Heart Interaction after Cerebral Ischemic Stroke

verfasst von: Jieli Chen, Chengcheng Cui, Xiaoping Yang, Jiang Xu, Poornima Venkat, Alex Zacharek, Peng Yu, Michael Chopp

Erschienen in: Translational Stroke Research | Ausgabe 4/2017

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Abstract

Cardiovascular diseases are approximately three times higher in patients with neurological deficits than in patients without neurological deficits. MicroRNA-126 (MiR-126) facilitates vascular remodeling and decreases fibrosis and is emerging as an important factor in the pathogenesis of cardiovascular diseases and cerebral stroke. In this study, we tested the hypothesis that decreased miR-126 after ischemic stroke may play an important role in regulating cardiac function. Wild-type (WT), specific conditional-knockout endothelial cell miR-126 (miR-126^EC−/−), and miR-126 knockout control (miR-126^fl/fl) mice were subjected to distal middle cerebral artery occlusion (dMCAo) (n = 10/group). Cardiac hemodynamics and function were measured using transthoracic Doppler echocardiography. Mice were sacrificed at 28 days after dMCAo. WT mice subjected to stroke exhibited significantly decreased cardiac ejection fraction and increased myocyte hypertrophy, fibrosis as well as increased heart inflammation, infiltrating macrophages, and oxidative stress compared to non-stroke animals. Stroke significantly decreased serum and heart miR-126 expression and increased miR-126 target genes, vascular cell adhesion protein-1, and monocyte chemotactic protein-1 gene, and protein expression in the heart compared to non-stroke mice. MiR-126^EC−/− mice exhibited significantly decreased cardiac function and increased cardiomyocyte hypertrophy, fibrosis, and inflammatory factor expression after stroke compared to miR-126^fl/fl stroke mice. Exosomes derived from endothelial cells of miR-126^EC−/− (miR-126^EC−/−EC-Exo) mice exhibited significantly decreased miR-126 expression than exosomes derived from miR-126^fl/fl (miR-126^fl/fl-EC-Exo) mice. Treatment of cardiomyocytes subjected to oxygen glucose deprivation with miR-126^fl/fl-EC-Exo exhibited significantly decreased hypertrophy than with miR-126^EC−/−EC-Exo treatment. Ischemic stroke directly induces cardiac dysfunction. Decreasing miR-126 expression may contribute to cardiac dysfunction after stroke in mice.

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Titel: MiR-126 Affects Brain-Heart Interaction after Cerebral Ischemic Stroke
verfasst von: Jieli Chen
Chengcheng Cui
Xiaoping Yang
Jiang Xu
Poornima Venkat
Alex Zacharek
Peng Yu
Michael Chopp
Publikationsdatum: 19.01.2017
Verlag: Springer US
Erschienen in: Translational Stroke Research / Ausgabe 4/2017
Print ISSN: 1868-4483
Elektronische ISSN: 1868-601X
DOI: https://doi.org/10.1007/s12975-017-0520-z

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MiR-126 Affects Brain-Heart Interaction after Cerebral Ischemic Stroke

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