Increasing Ang1/Tie2 expression by simvastatin treatment induces vascular stabilization and neuroblast migration after stroke

Autor: Alex Zacharek, Jieli Chen, Xu Cui, Michael Chopp
Rok vydání: 2009
Předmět:
Doublecortin Domain Proteins
Male
Simvastatin
Angiogenesis
Pharmacology
Brain Ischemia
Brain ischemia
0302 clinical medicine
Cell Movement
polycyclic compounds
Neurons
vascular stabilization
0303 health sciences
biology
Articles
Receptor
TIE-2
stroke
3. Good health
Endothelial stem cell
Tie2
medicine.anatomical_structure
Blood-Brain Barrier
cardiovascular system
Molecular Medicine
Microtubule-Associated Proteins
medicine.drug
Doublecortin Protein
Neovascularization
Physiologic
Subventricular zone
angiopoietin 1
03 medical and health sciences
Neuroblast
Occludin
Neuroblast migration
Angiopoietin-1
medicine
Animals
cardiovascular diseases
Rats
Wistar
030304 developmental biology
Neuropeptides
Endothelial Cells
Membrane Proteins
nutritional and metabolic diseases
Cell Biology
medicine.disease
Rats
Doublecortin
Gene Expression Regulation
nervous system
Immunology
biology.protein
Blood Vessels
030217 neurology & neurosurgery
Zdroj: Journal of Cellular and Molecular Medicine
ISSN: 1582-4934
1582-1838
DOI: 10.1111/j.1582-4934.2008.00380.x
Popis: In this study, we tested the hypothesis that the Angiopoietin 1 (Ang1)/Tie2 pathway mediates simvastatin-induced vascular integrity and migration of neuroblasts after stroke. Rats were subjected to 2 hrs of middle cerebral artery occlusion (MCAo) and treated, starting 1 day after stroke with or without simvastatin (1 mg/kg, daily) for 7 days. Simvastatin treatment significantly decreased blood–brain barrier (BBB) leakage and concomitantly, increased Ang1, Tie2 and Occludin expression in the ischaemic border (IBZ) compared to the MCAo control group. Simvastatin also significantly increased doublecortin (DCX, a marker of migrating neuroblasts) expression in the IBZ compared to control MCAo rats. DCX was highly expressed around vessels. To further investigate the signalling pathway of simvastatin-induced vascular stabilization and angiogenesis, rat brain microvascular endothelial cell (RBMEC) culture was employed. The data show that simvastatin treatment of RBMEC increased Ang1 and Tie2 gene and protein expression and promoted phosphorylated-Tie2 activity. Simvastatin significantly increased endothelial capillary tube formation, an index of angiogenesis, compared to non-treated control. Inhibition of Ang1 or knockdown of Tie2 gene expression in endothelial cells significantly attenuated simvastatin-induced capillary tube formation. In addition, simvastatin significantly increased subventricular zone (SVZ) explant cell migration compared to non-treatment control. Inhibition of Ang1 significantly attenuated simvastatin-induced SVZ cell migration. Simvastatin treatment of stroke increases Ang1/Tie2 expression and thereby reduces BBB leakage and promotes vascular stabilization. Ang1/Tie2 expression induced by simvastatin treatment promotes neuroblast micro-vascular coupling after stroke.
Databáze: OpenAIRE
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