Neuregulin-1 attenuates neointimal formation following vascular injury and inhibits the proliferation of vascular smooth muscle cells.
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.
Clement
Ceiléssia M
CM
Department of Anatomy and Neurobiology, Neuroscience Institute, Morehouse School of Medicine, Atlanta, GA 30310, USA.
Thomas
LaReese K
LK
Mou
Yongsang
Y
Croslan
DaJoie R
DR
Gibbons
Gary H
GH
Ford
Byron D
BD
D000818:Animals; D001011:Aorta / Q000166:cytology; D002340:Carotid Artery Diseases / Q000473:pathology / Q000628:therapy*; D020212:Carotid Artery Injuries / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D002404:Catheterization / Q000009:adverse effects*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D066246:ErbB Receptors / Q000378:metabolism; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism* / Q000494:pharmacology; D020890:Neuregulin-1; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D066247:Receptor, ErbB-4; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; C490580:Nrg1 protein, rat; D010982:Platelet-Derived Growth Factor; D066246:ErbB Receptors; C587691:Erbb4 protein, rat; D066247:Receptor, ErbB-4; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3