| Spatial heterogeneity of endothelial phenotypes correlates with side-specific vulnerability to calcification in normal porcine aortic valves. | |
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MedLine Citation:
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PMID: 15761200 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Calcific aortic valve sclerosis involves inflammatory processes and occurs preferentially on the aortic side of endothelialized valve leaflets. Although the endothelium is recognized to play critical roles in focal vascular sclerosis, the contributions of valvular endothelial phenotypes to aortic valve sclerosis and side-specific susceptibility to calcification are poorly understood. Using RNA amplification and cDNA microarrays, we identified 584 genes as differentially expressed in situ by the endothelium on the aortic side versus ventricular side of normal adult pig aortic valves. These differential transcriptional profiles, representative of the steady state in vivo, identify globally distinct endothelial phenotypes on opposite sides of the aortic valve. Several over-represented biological classifications with putative relevance to endothelial regulation of valvular homeostasis and aortic-side vulnerability to calcification were identified among the differentially expressed genes. Of note, multiple inhibitors of cardiovascular calcification were significantly less expressed by endothelium on the disease-prone aortic side of the valve, suggesting side-specific permissiveness to calcification. However, coexisting putative protective mechanisms were also expressed. Specifically, enhanced antioxidative gene expression and the lack of differential expression of proinflammatory molecules on the aortic side may protect against inflammation and lesion initiation in the normal valve. These data implicate the endothelium in regulating valvular calcification and suggest that spatial heterogeneity of valvular endothelial phenotypes may contribute to the focal susceptibility for lesion development. |
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Authors:
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Craig A Simmons; Gregory R Grant; Elisabetta Manduchi; Peter F Davies |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. Date: 2005-03-10 |
Journal Detail:
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Title: Circulation research Volume: 96 ISSN: 1524-4571 ISO Abbreviation: Circ. Res. Publication Date: 2005 Apr |
Date Detail:
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Created Date: 2005-04-15 Completed Date: 2005-10-11 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 0047103 Medline TA: Circ Res Country: United States |
Other Details:
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Languages: eng Pagination: 792-9 Citation Subset: IM |
Affiliation:
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Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia PA 19104, USA. c.simmons@utoronto.ca |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antioxidants / metabolism Aortic Valve* Bone Morphogenetic Protein 4 Bone Morphogenetic Proteins / genetics Calcinosis / etiology* Endothelial Cells / physiology* Gene Expression Profiling Glycoproteins / physiology Heart Valve Diseases / etiology* Hemodynamics Inflammation / complications Male NF-kappa B / physiology Osteoprotegerin Phenotype Receptors, Cytoplasmic and Nuclear / physiology Receptors, Tumor Necrosis Factor / physiology Swine |
| Grant Support | |
ID/Acronym/Agency:
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HL36049/HL/NHLBI NIH HHS; HL62250/HL/NHLBI NIH HHS; HL64388/HL/NHLBI NIH HHS; K25 HG000052-03/HG/NHGRI NIH HHS; K25 HG002296-01/HG/NHGRI NIH HHS; K25-HG-00052/HG/NHGRI NIH HHS; K25-HG-02296/HG/NHGRI NIH HHS; P01 HL062250-100005/HL/NHLBI NIH HHS; R01 HL064388-01A1/HL/NHLBI NIH HHS; R37 HL036049-16/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antioxidants; 0/Bone Morphogenetic Protein 4; 0/Bone Morphogenetic Proteins; 0/Glycoproteins; 0/NF-kappa B; 0/Osteoprotegerin; 0/Receptors, Cytoplasmic and Nuclear; 0/Receptors, Tumor Necrosis Factor |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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