| Chronic hypoxia and VEGF differentially modulate abundance and organization of myosin heavy chain isoforms in fetal and adult ovine arteries. | |
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MedLine Citation:
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PMID: 22992677 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Chronic hypoxia increases vascular endothelial growth factor (VEGF) and thereby promotes angiogenesis. The present study explores the hypothesis that hypoxic increases in VEGF also remodel artery wall structure and contractility through phenotypic transformation of smooth muscle. Pregnant and nonpregnant ewes were maintained at sea level (normoxia) or 3,820 m (hypoxia) for the final 110 days of gestation. Common carotid arteries harvested from term fetal lambs and nonpregnant adults were denuded of endothelium and studied in vitro. Stretch-dependent contractile stresses were 32 and 77% of normoxic values in hypoxic fetal and adult arteries. Hypoxic hypocontractility was coupled with increased abundance of nonmuscle myosin heavy chain (NM-MHC) in fetal (+37%) and adult (+119%) arteries. Conversely, hypoxia decreased smooth muscle MHC (SM-MHC) abundance by 40% in fetal arteries but increased it 123% in adult arteries. Hypoxia decreased colocalization of NM-MHC with smooth muscle α-actin (SM-αA) in fetal arteries and decreased colocalization of SM-MHC with SM-αA in adult arteries. Organ culture with physiological concentrations (3 ng/ml) of VEGF-A(165) similarly depressed stretch-dependent stresses to 37 and 49% of control fetal and adult values. The VEGF receptor antagonist vatalanib ablated VEGF's effects in adult but not fetal arteries, suggesting age-dependent VEGF receptor signaling. VEGF replicated hypoxic decreases in colocalization of NM-MHC with SM-αA in fetal arteries and decreases in colocalization of SM-MHC with SM-αA in adult arteries. These results suggest that hypoxic increases in VEGF not only promote angiogenesis but may also help mediate hypoxic arterial remodeling through age-dependent changes in smooth muscle phenotype and contractility. |
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Authors:
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Margaret C Hubbell; Andrew J Semotiuk; Richard B Thorpe; Olayemi O Adeoye; Stacy M Butler; James M Williams; Omid Khorram; William J Pearce |
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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 Date: 2012-09-19 |
Journal Detail:
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Title: American journal of physiology. Cell physiology Volume: 303 ISSN: 1522-1563 ISO Abbreviation: Am. J. Physiol., Cell Physiol. Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-19 Completed Date: 2013-01-22 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 100901225 Medline TA: Am J Physiol Cell Physiol Country: United States |
Other Details:
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Languages: eng Pagination: C1090-103 Citation Subset: IM |
Affiliation:
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Divisions of Physiology, Pharmacology, and Biochemistry, Center for Perinatal Biology, Loma Linda University Schoolof Medicine, Loma Linda, California 92350, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Anoxia / physiopathology* Arteries / embryology, metabolism* Female Fetus / blood supply Myosin Heavy Chains / genetics, metabolism* Oxygen / metabolism Phthalazines / pharmacology Pregnancy Protein Kinase Inhibitors / pharmacology Protein Transport Pyridines / pharmacology Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors Sheep / embryology*, physiology* Vascular Endothelial Growth Factor A / pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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P01 HD031226/HD/NICHD NIH HHS; P01-HD-31226/HD/NICHD NIH HHS; R01 HL054120/HL/NHLBI NIH HHS; R01 NS076945/NS/NINDS NIH HHS; R01-HL-54120/HL/NHLBI NIH HHS; R01-HL-64867/HL/NHLBI NIH HHS; R01-NS-076945/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Myosin Heavy Chains; 0/Phthalazines; 0/Protein Kinase Inhibitors; 0/Pyridines; 0/Vascular Endothelial Growth Factor A; 5DX9U76296/vatalanib; 7782-44-7/Oxygen; EC 2.7.10.1/Receptors, Vascular Endothelial Growth Factor |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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