Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 29, Issue 5, Pages 911-920Publisher
SAGE PUBLICATIONS INC
DOI: 10.1038/jcbfm.2009.11
Keywords
arteriogenesis; CBF; Niaspan; stroke; TACE
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Funding
- National Institute of Neurological Disorders and Stroke [RO1 NS047682, PO1 NS23393, RO1 AG031811]
- American Heart Association [0750048Z]
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We tested the hypothesis that Niaspan (a prolonged release formulation of niacin) increases tumor necrosis factor-alpha-converting enzyme (TACE) expression and Notch signaling activity and promotes arteriogenesis after stroke. Rats were subjected to middle cerebral artery occlusion and were treated with or without Niaspan. Niaspan significantly elevated local cerebral blood flow, and increased arteriogenesis as indicated by increased arterial diameter and vascular smooth muscle cell (VSMC) proliferation in the ischemic brain after stroke. The increased arteriogenesis significantly correlated with the functional outcome after stroke. Niaspan treatment of stroke upregulated TACE, Notch1, and Notch intracellular domain expression in the ischemic brain. To further investigate the mechanisms of Niaspan-induced arteriogenesis, a primary brain arterial culture was used. Niacin treatment significantly increased arterial sprouting and VSMC migration compared with control nontreated arterial cells. Inhibition of TACE by the TACE inhibitor or knockdown of TACE gene expression in brain arterial culture significantly attenuated Niacin-induced arterial sprouting and VSMC migration. In addition, TACE treatment of arterial culture significantly increased arterial VSMC migration and arterial sprouting. Knockdown of Notch1 marginally decreased arterial sprouting and VSMC migration compared with scrambled control. Niaspan promotes arteriogenesis, which is mediated, in part, by TACE. Journal of Cerebral Blood Flow & Metabolism (2009) 29, 911-920; doi:10.1038/jcbfm.2009.11; published online 18 February 2009
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