Document Detail


Niaspan increases angiogenesis and improves functional recovery after stroke.
MedLine Citation:
PMID:  17557352     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: High-density lipoprotein (HDL) is implicated in the modulation of angiogenesis. In this study, we investigated whether the Niacin-mediated increase of HDL regulates angiogenesis and thereby improves functional outcome after stroke. METHODS: Adult male rats were subjected to middle cerebral artery occlusion and were treated with or without different doses (40 and 80 mg/kg) of Niaspan, starting 24 hours after middle cerebral artery occlusion and daily for 14 days. Neurological functional tests were performed, and serum HDL level was measured. Angiogenesis and angiogenic factor expression were measured by immunohistochemistry, corneal neovascularization and capillary tube formation assay, and Western blot, respectively. RESULTS: Niaspan significantly increased HDL level, promoted angiogenesis in the ischemic brain, and improved functional outcome after stroke. Niaspan also significantly increased corneal neovascularization compared with nontreatment control. Mechanisms underlying the Niaspan-induced vascular remodeling were investigated. Niaspan increased the expression of vascular endothelial growth factor and angiopoietin-1 (Ang1), and phosphorylation of Akt, endothelial nitric oxide synthase (NOS), and Tie2 in the ischemic brain. Niacin upregulated Ang1 expression in cultured brain endothelial cells and increased vascular endothelial growth factor, Ang1, and endothelial NOS expression in cultured astrocytes, and dose-dependently increased capillary tube formation compared with nontreatment control. Inhibition of NOS partially decreased Niacin-induced capillary tube formation. Inhibition of phosphoinositide 3-kinase or knockdown of Tie2 substantially and significantly decreased Niacin-induced capillary tube formation. INTERPRETATION: Niacin increases HDL and promotes angiogenesis, which may contribute to improvement of functional outcome after stroke. The Ang1/Tie2, phosphoinositide 3-kinase/Akt, and endothelial NOS pathways appear to mediate Niacin-induced angiogenesis.
Authors:
Jieli Chen; Xu Cui; Alex Zacharek; Hao Jiang; Cynthia Roberts; Chunling Zhang; Mei Lu; Alissa Kapke; Carolyn S Feldkamp; Michael Chopp
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Annals of neurology     Volume:  62     ISSN:  0364-5134     ISO Abbreviation:  Ann. Neurol.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-08-02     Completed Date:  2007-10-12     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7707449     Medline TA:  Ann Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  49-58     Citation Subset:  IM    
Affiliation:
Department of Neurology, Henry Ford Hospital, 2799 West Grand Boulevard, Detroit, MI 48202, USA.
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MeSH Terms
Descriptor/Qualifier:
Angiopoietin-1 / metabolism
Animals
Bromodeoxyuridine / metabolism
Cells, Cultured
Cholesterol / blood
Cholesterol, HDL / blood
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Delivery Systems / methods
Endothelial Growth Factors / metabolism
Gene Expression Regulation / drug effects
Male
Neovascularization, Physiologic / drug effects*
Niacin / therapeutic use*
Nitric Oxide Synthase Type III / metabolism
Oncogene Protein v-akt / metabolism
Rats
Rats, Wistar
Recovery of Function / drug effects*
Stroke / drug therapy*,  physiopathology
Vitamin B Complex / therapeutic use*
Grant Support
ID/Acronym/Agency:
P01 NS 23393/NS/NINDS NIH HHS; R01 NS 047682/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Angiopoietin-1; 0/Cholesterol, HDL; 0/Endothelial Growth Factors; 12001-76-2/Vitamin B Complex; 57-88-5/Cholesterol; 59-14-3/Bromodeoxyuridine; 59-67-6/Niacin; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 2.7.11.1/Oncogene Protein v-akt

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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