Document Detail


The role of alpha and beta platelet-derived growth factor receptor in the vascular response to injury in nonhuman primates.
MedLine Citation:
PMID:  10195916     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Restenosis remains a significant clinical problem associated with mechanical interventional procedures for arterial revascularization or repair, including coronary angioplasty and stenting. Studies with rodents have established that platelet-derived growth factor (PDGF), a potent chemotactic and mitogenic agent for vascular smooth muscle cells, is a key mediator of lesion formation after vascular injury. To further explore this hypothesis in a more clinically relevant model, neutralizing monoclonal antibodies (mAbs) were used to examine the effect of selective inhibition of alpha or beta PDGF receptor (PDGFR) on neointima formation in nonhuman primates. Carotid arteries were injured by surgical endarterectomy and femoral arteries by balloon catheter dilatation. Immunostaining revealed that both injuries induced cell proliferation and the upregulation of beta PDGFR but not alpha PDGFR. By 7 days after injury, beta PDGFR staining was limited to the luminal region of the media, the small areas of neointima, and the adventitia. Nearly all bromodeoxyuridine-positive cells were found in these regions as well. After 30 days, a concentric neointima that stained strongly for beta PDGFR had formed in the carotid and femoral arteries. Treatment of baboons with anti-beta PDGFR mAb 2A1E2 for 6 days after injury reduced the carotid artery and femoral artery lesion sizes by 37% (P<0.05) and 48% (P<0.005), respectively, when measured at 30 days. Under the same conditions, treatment with anti-alpha PDGFR mAb 2H7C5 had no effect. These findings suggest that PDGF mediates neointima formation through the beta PDGFR, and that antagonism of this pathway may be a promising therapeutic strategy for reducing clinical restenosis.
Authors:
N A Giese; M M Marijianowski; O McCook; A Hancock; V Ramakrishnan; L J Fretto; C Chen; A B Kelly; J A Koziol; J N Wilcox; S R Hanson
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  19     ISSN:  1079-5642     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  1999 Apr 
Date Detail:
Created Date:  1999-05-17     Completed Date:  1999-05-17     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  900-9     Citation Subset:  IM    
Affiliation:
COR Therapeutics Inc, South San Francisco, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Blocking / pharmacology
Antibodies, Monoclonal / pharmacology
Balloon Dilatation
Carotid Arteries / pathology
Carotid Artery Injuries*
Cell Division / immunology
Endarterectomy
Femoral Artery / injuries*,  pathology
Male
Papio
Phosphorylation
Receptor, Platelet-Derived Growth Factor alpha
Receptor, Platelet-Derived Growth Factor beta
Receptors, Platelet-Derived Growth Factor / antagonists & inhibitors,  biosynthesis,  immunology,  physiology*
Tunica Intima / immunology,  pathology
Grant Support
ID/Acronym/Agency:
HL-31469/HL/NHLBI NIH HHS; HL-47838/HL/NHLBI NIH HHS; RR-00165/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Blocking; 0/Antibodies, Monoclonal; EC 2.7.10.1/Receptor, Platelet-Derived Growth Factor alpha; EC 2.7.10.1/Receptor, Platelet-Derived Growth Factor beta; EC 2.7.10.1/Receptors, Platelet-Derived Growth Factor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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