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.
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: Jullet Han; Julia Pollak; Tao Yang; Mohammad R Siddiqui; Kristian P Doyle; Kereshmeh Taravosh-Lahn; Egle Cekanaviciute; Alex Han; Jeremy Z Goodman; Britta Jones; Deqiang Jing; Stephen M Massa; Frank M Longo; Marion S Buckwalter Journal: Stroke Date: 2012-04-24 Impact factor: 7.914
Authors: Tarek K Motawi; Hebatallah A Darwish; Manal A Hamed; Nagy S El-Rigal; Asmaa F Aboul Naser Journal: Metab Brain Dis Date: 2017-05-30 Impact factor: 3.584