| Anatomic closure of the premature patent ductus arteriosus: The role of CD14+/CD163+ mononuclear cells and VEGF in neointimal mound formation. | |
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MedLine Citation:
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PMID: 21691249 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Pediatric research Volume: 70 ISSN: 1530-0447 ISO Abbreviation: Pediatr. Res. Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-09-02 Completed Date: 2011-12-19 Revised Date: 2013-02-08 |
Medline Journal Info:
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Nlm Unique ID: 0100714 Medline TA: Pediatr Res Country: United States |
Other Details:
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Languages: eng Pagination: 332-8 Citation Subset: IM |
Affiliation:
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Pharmaceutical Discovery Division, SRI International, Menlo Park, California 94025, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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 HL046691-16/HL/NHLBI NIH HHS; U01 HL056061-12/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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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 | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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