Niaspan increases angiogenesis and improves functional recovery after stroke
Abstract
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 80mg/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. Ann Neurol 2007
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In rats with cerebral ischaemia, vitamin B3 administration, which raises HDL and lowers serum cholesterol, increased angiogenesis, VEGF and angiopoietin 1 expression, and phosphorylation of eNOS and Tie2, improving neurological recovery.
“In rats with cerebral ischaemia, vitamin B3 administration, which elevates high-density lipoprotein and thereby reduces serum cholesterol, increased angiogenesis, the expression of VEGF and angiopoietin 1, and enhanced the phosphorylation (ie, activation) of eNOS and the angiopoietin-1 receptor Tie2, thus improving neurological recovery.85”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [85]
In cerebral endothelial cell culture, eNOS inhibition or Tie2 knockdown reduced the effects of vitamin B3 on capillary tube formation, showing a role for eNOS and angiopoietin 1 in the beneficial effects of HDL elevation.
“In cerebral endothelial cell culture, the effects of vitamin B3 on capillary tube formation were reduced after eNOS inhibition or Tie2 knockdown,85 showing a role for eNOS and angiopoietin 1 in the beneficial effects of the high-density lipoprotein elevation.”
From Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation (2012) · cites this paper as [85]
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- Authors
- Chen, J., Cui, X., Zacharek, A., Jiang, H., Roberts, C., Zhang, C., Lu, M., Kapke, A., Feldkamp, C. S., & Chopp, M.
- Affiliations
- Henry Ford Health (US)
- Henry Ford Hospital (US)
- Corresponding author
- Chopp, Michael
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2007-06-07
- Volume
- 62
- Issue
- 1
- Pages
- 49-58
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2150253311
- Cited by
- 105
- References
- 49
- Citations by year
- 2026: 3 · 2024: 1 · 2023: 2 · 2022: 5 · 2021: 4 · 2020: 1 · 2019: 7 · 2018: 1 · 2017: 4 · 2016: 9 · 2015: 7 · 2014: 14 · 2013: 8 · 2012: 10
- FWCI
- 2.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS047682, P01NS23393, P01NS023393)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- Niaspan, nicotinic acid, high-density lipoprotein, angiogenesis, stroke, middle cerebral artery occlusion, functional recovery, angiopoietin-1, Tie2, vascular endothelial growth factor, endothelial nitric oxide synthase, phosphatidylinositol 3-kinase/Akt signaling, capillary tube formation, corneal neovascularization, ischemic brain, astrocytes, brain endothelial cells, vascular remodeling
- MeSH terms
- Animals, Bromodeoxyuridine, Cells, Cultured, Cholesterol, Disease Models, Animal, Dose-Response Relationship, Drug, Gene Expression Regulation, Cholesterol, HDL, Male, Niacin, Vitamin B Complex, Endothelial Growth Factors, Drug Delivery Systems, Rats, Wistar, Neovascularization, Physiologic, Recovery of Function, Stroke, Angiopoietin-1, Oncogene Protein v-akt, Rats, Nitric Oxide Synthase Type III
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