Source:http://linkedlifedata.com/resource/pubmed/id/18096704
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
9
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| pubmed:dateCreated |
2008-2-25
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| pubmed:abstractText |
Hyperglycemia is an independent risk factor for development of vascular diabetic complications. Vascular dysfunction in diabetics manifests in a tissue-specific manner; macrovasculature is affected by atherosclerotic lesions, and microvascular complications are described as "aberrant angiogenesis": in the same patient angiogenesis is increased in some tissues (e.g. retinal neovascularization) and decreased in others (e.g. in skin). Molecular cell- and tissue-specific mechanisms regulating the response of vasculature to hyperglycemia remain unclear. Thrombospondin-1 (TSP-1), a potent antiangiogenic and proatherogenic protein, has been implicated in the development of several vascular diabetic complications (atherosclerosis, nephropathy, and cardiomyopathy). This study examines cell type-specific regulation of production of thrombospondin-1 by high glucose. We previously reported the increased expression of TSP-1 in the large arteries of diabetic animals. mRNA and protein levels were up-regulated in response to high glucose. Unlike in macrovascular cells, TSP-1 protein levels are dramatically decreased in response to high glucose in microvascular endothelial cells and retinal pigment epithelial cells (RPE). This down-regulation is post-transcriptional; mRNA levels are increased. In situ mRNA hybridization and immunohistochemistry revealed that the level of mRNA is up-regulated in RPE of diabetic rats, whereas the protein level is decreased. This cell type-specific posttranscriptional suppression of TSP-1 production in response to high glucose in microvascular endothelial cells and RPE is controlled by untranslated regions of TSP-1 mRNA that regulate coupling of TSP-1 mRNA to polysomes and its translation. The cell-specific regulation of TSP-1 suggests a potential mechanism for the aberrant angiogenesis in diabetics and TSP-1 involvement in development of various vascular diabetic complications.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Feb
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
29
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| pubmed:volume |
283
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
5699-707
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| pubmed:meshHeading |
pubmed-meshheading:18096704-Angiogenesis Inhibitors,
pubmed-meshheading:18096704-Animals,
pubmed-meshheading:18096704-Atherosclerosis,
pubmed-meshheading:18096704-Cattle,
pubmed-meshheading:18096704-Cells, Cultured,
pubmed-meshheading:18096704-Diabetes Complications,
pubmed-meshheading:18096704-Down-Regulation,
pubmed-meshheading:18096704-Endothelial Cells,
pubmed-meshheading:18096704-Glucose,
pubmed-meshheading:18096704-Humans,
pubmed-meshheading:18096704-Hyperglycemia,
pubmed-meshheading:18096704-In Situ Hybridization,
pubmed-meshheading:18096704-Neovascularization, Pathologic,
pubmed-meshheading:18096704-Organ Specificity,
pubmed-meshheading:18096704-Pigment Epithelium of Eye,
pubmed-meshheading:18096704-Protein Biosynthesis,
pubmed-meshheading:18096704-Rats,
pubmed-meshheading:18096704-Rats, Zucker,
pubmed-meshheading:18096704-Sweetening Agents,
pubmed-meshheading:18096704-Thrombospondin 1
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| pubmed:year |
2008
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| pubmed:articleTitle |
Cell type-specific post-transcriptional regulation of production of the potent antiangiogenic and proatherogenic protein thrombospondin-1 by high glucose.
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| pubmed:affiliation |
Department of Molecular Cardiology and Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Cleveland Clinic, Cleveland, Ohio 44026, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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