Document Detail


Anatomic closure of the premature patent ductus arteriosus: The role of CD14+/CD163+ mononuclear cells and VEGF in neointimal mound formation.
MedLine Citation:
PMID:  21691249     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Permanent closure of the newborn ductus arteriosus requires the development of neointimal mounds to completely occlude its lumen. VEGF is required for neointimal mound formation. The size of the neointimal mounds (composed of proliferating endothelial and migrating smooth muscle cells) is directly related to the number of VLA4 mononuclear cells that adhere to the ductus lumen after birth. We hypothesized that VEGF plays a crucial role in attracting CD14/CD163 mononuclear cells (expressing VLA4) to the ductus lumen and that CD14/CD163 cell adhesion to the ductus lumen is important for neointimal growth. We used neutralizing antibodies against VEGF and VLA-4 to determine their respective roles in remodeling the ductus of premature newborn baboons. Anti-VEGF treatment blocked CD14/CD163 cell adhesion to the ductus lumen and prevented neointimal growth. Anti-VLA-4 treatment blocked CD14/CD163 cell adhesion to the ductus lumen, decreased the expression of PDGF-B (which promotes smooth muscle migration), and blocked smooth muscle influx into the neointimal subendothelial space (despite the presence of increased VEGF in the ductus wall). We conclude that VEGF is necessary for CD14/CD163 cell adhesion to the ductus lumen and that CD14/CD163 cell adhesion is essential for VEGF-induced expansion of the neointimal subendothelial zone.
Authors:
Nahid Waleh; Steven Seidner; Donald McCurnin; Luis Giavedoni; Vida Hodara; Susan Goelz; Bao Mei Liu; Christine Roman; Ronald I Clyman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pediatric research     Volume:  70     ISSN:  1530-0447     ISO Abbreviation:  Pediatr. Res.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-02     Completed Date:  2011-12-19     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  0100714     Medline TA:  Pediatr Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  332-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn
Antibodies, Neutralizing / metabolism
Antigens, CD / metabolism*
Antigens, CD14 / metabolism*
Antigens, Differentiation, Myelomonocytic / metabolism*
Cell Adhesion / physiology
Cell Movement / physiology
Ductus Arteriosus, Patent / metabolism,  pathology*
Female
Humans
Hypoxia-Inducible Factor 1, alpha Subunit / genetics,  metabolism
Infant, Newborn
Integrin alpha4beta1 / metabolism
Leukocytes, Mononuclear / metabolism*
Neointima*
Nitric Oxide Synthase Type III / metabolism
Papio
Receptors, Cell Surface / metabolism*
Vascular Cell Adhesion Molecule-1 / metabolism
Vascular Endothelial Growth Factor A / metabolism*
Grant Support
ID/Acronym/Agency:
C06 RR12087/RR/NCRR NIH HHS; HL46691/HL/NHLBI NIH HHS; HL52636/HL/NHLBI NIH HHS; HL56061/HL/NHLBI NIH HHS; P51RR13986/RR/NCRR NIH HHS; R01 HL046691/HL/NHLBI NIH HHS; R01 HL046691-16/HL/NHLBI NIH HHS; U01 HL056061/HL/NHLBI NIH HHS; U01 HL056061-12/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Neutralizing; 0/Antigens, CD; 0/Antigens, CD14; 0/Antigens, Differentiation, Myelomonocytic; 0/CD163 antigen; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/Integrin alpha4beta1; 0/Receptors, Cell Surface; 0/Vascular Cell Adhesion Molecule-1; 0/Vascular Endothelial Growth Factor A; EC 1.14.13.39/Nitric Oxide Synthase Type III
Comments/Corrections

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