title: MiR-126 Affects Brain-Heart Interaction after Cerebral Ischemic Stroke.
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-126EC-/-), and miR-126 knockout control (miR-126fl/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-126EC-/-mice exhibited significantly decreased cardiac function and increased cardiomyocyte hypertrophy, fibrosis, and inflammatory factor expression after stroke compared to miR-126fl/flstroke mice. Exosomes derived from endothelial cells of miR-126EC-/-(miR-126EC-/-EC-Exo) mice exhibited significantly decreased miR-126 expression than exosomes derived from miR-126fl/fl(miR-126fl/fl-EC-Exo) mice. Treatment of cardiomyocytes subjected to oxygen glucose deprivation with miR-126fl/fl-EC-Exo exhibited significantly decreased hypertrophy than with miR-126EC-/-EC-Exo treatment. Ischemic stroke directly induces cardiac dysfunction. Decreasing miR-126 expression may contribute to cardiac dysfunction after stroke in mice.
authors.affiliation: Henry Ford Hospital Neurology, Detroit, MI, 48202, USA. jieli@neuro.hfh.edu.|Gerontology Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China. jieli@neuro.hfh.edu.
authors.forename: Jieli
authors.identifier: 0000-0001-5446-9101
authors.initials: J
authors.lastname: Chen
authors.affiliation: Henry Ford Hospital Neurology, Detroit, MI, 48202, USA.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Cui
authors.affiliation: Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, MI, 48202, USA.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Yang
authors.affiliation: Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, MI, 48202, USA.
authors.forename: Jiang
authors.initials: J
authors.lastname: Xu
authors.affiliation: Henry Ford Hospital Neurology, Detroit, MI, 48202, USA.
authors.forename: Poornima
authors.initials: P
authors.lastname: Venkat
authors.affiliation: Henry Ford Hospital Neurology, Detroit, MI, 48202, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Zacharek
authors.affiliation: Henry Ford Hospital Neurology, Detroit, MI, 48202, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Yu
authors.affiliation: Henry Ford Hospital Neurology, Detroit, MI, 48202, USA.|Department of Physics, Oakland University, Rochester, MI, 48309, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000235:genetics; D006331:Heart Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D000074662:NADPH Oxidase 2 / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D000199:Actins; D018932:Chemokine CCL2; C545201:MIRN126 microRNA, mouse; D035683:MicroRNAs; D016212:Transforming Growth Factor beta; D019010:Vascular Cell Adhesion Molecule-1; D000074662:NADPH Oxidase 2
keywords: Brain-heart interaction; Cardiac dysfunction; Cardiomyocyte; Ischemia; MicroRNA-126; Stroke