Journal
JOURNAL OF VASCULAR RESEARCH
Volume 44, Issue 4, Pages 303-312Publisher
KARGER
DOI: 10.1159/000101776
Keywords
angioplasty; erbB receptor; vascular injury; vascular smooth muscle cells; restenosis; atherosclerosis
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Funding
- NCRR NIH HHS [C06 RR-07571] Funding Source: Medline
- NHLBI NIH HHS [HL067702, HL003676] Funding Source: Medline
- NINDS NIH HHS [NS34194] Funding Source: Medline
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [T32HL067702] Funding Source: NIH RePORTER
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Neuregulin-1 ( NRG-1) is expressed in vascular endothelial cells, and its receptors are localized to the underlying smooth muscle cells. However, the role of NRG-1 in vascular function and injury is largely unknown. First, the expression of NRG-1 and its receptors ( erbB receptors) was analyzed after balloon injury to the rat carotid artery. NRG-1 and erbB expression levels were low in uninjured vessels; however, NRG-1 and erbB4 were upregulated following injury. We then examined the effect of NRG-1 on neointimal formation following balloon injury. NRG-1 was administered by tail-vein injection prior to injury and every 2 days following injury. Two weeks after injury, NRG-1-treated animals demonstrated a 50% reduction in lesion size compared with controls receiving the vehicle. To examine possible mechanisms for NRG-1 action, we examined its effects on vascular smooth muscle cell ( VSMC) function. Rat VSMC cultures were pretreated with NRG- 1 for 24 h and then stimulated with platelet- derived growth factor. NRG-1 significantly decreased platelet- derived growth factor- stimulated VSMC proliferation and migration. These findings suggest that NRG-1 may be a novel therapeutic candidate for the treatment of restenosis and atherosclerosis. Copyright (c) 2007 S. Karger AG, Basel
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