Niaspan increases angiogenesis and improves functional recovery after stroke

Area of Science:

• Neuroscience
• Cardiovascular Research
• Regenerative Medicine

Background:

• High-density lipoprotein (HDL) plays a role in regulating angiogenesis.
• The impact of Niacin-mediated HDL increase on post-stroke angiogenesis and functional recovery remains to be fully elucidated.

Purpose of the Study:

• To investigate if Niacin-mediated increase in HDL levels influences angiogenesis and improves functional outcomes following stroke.
• To explore the molecular mechanisms underlying Niacin's effects on vascular remodeling and angiogenesis.

Main Methods:

• Middle cerebral artery occlusion was induced in adult male rats, followed by treatment with varying doses of Niaspan (40 and 80 mg/kg).
• Neurological function, serum HDL levels, angiogenesis, and angiogenic factor expression were assessed using functional tests, biochemical assays, immunohistochemistry, corneal neovascularization assays, and Western blot analysis.
• In vitro studies involved cultured brain endothelial cells and astrocytes to examine Niacin's effects on angiogenic factor expression and capillary tube formation, with specific pathway inhibitors used.

Main Results:

• Niaspan significantly elevated HDL levels, enhanced angiogenesis in the ischemic brain, and improved functional recovery post-stroke.
• Corneal neovascularization was significantly increased in Niaspan-treated rats. Molecular analysis revealed increased expression of vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang1), and phosphorylation of Akt, endothelial nitric oxide synthase (eNOS), and Tie2.
• In vitro, Niacin upregulated Ang1 and VEGF expression in endothelial cells and astrocytes, dose-dependently increased capillary tube formation, and these effects were partially mediated by eNOS and significantly by the Ang1/Tie2 and PI3K/Akt pathways.

Conclusions:

• Niacin administration effectively increases HDL levels and promotes angiogenesis, contributing to improved functional outcomes after stroke.
• The Ang1/Tie2, PI3K/Akt, and eNOS signaling pathways are identified as key mediators of Niacin-induced angiogenesis.
• These findings highlight the potential of Niacin as a therapeutic agent for stroke recovery by leveraging its angiogenic properties.