| pubmed-article:8636110 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:8636110 | lifeskim:mentions | umls-concept:C0206745 | lld:lifeskim |
| pubmed-article:8636110 | lifeskim:mentions | umls-concept:C0034821 | lld:lifeskim |
| pubmed-article:8636110 | lifeskim:mentions | umls-concept:C0020443 | lld:lifeskim |
| pubmed-article:8636110 | lifeskim:mentions | umls-concept:C1421455 | lld:lifeskim |
| pubmed-article:8636110 | lifeskim:mentions | umls-concept:C1517499 | lld:lifeskim |
| pubmed-article:8636110 | pubmed:issue | 12 | lld:pubmed |
| pubmed-article:8636110 | pubmed:dateCreated | 1996-7-9 | lld:pubmed |
| pubmed-article:8636110 | pubmed:abstractText | We have used the technique of adenovirus-mediated gene transfer to study the in vivo function of the very low density lipoprotein receptor (VLDLR) in low density lipoprotein receptor (LDLR) knockout mice. We generated a replication-defective adenovirus (AdmVLDLR) containing mouse VLDLR cDNA driven by a cytomegalovirus promoter. Transduction of cultured Hepa (mouse hepatoma) cells and LDLR-deficient CHO-ldlA7 cells in vitro by the virus led to high-level expression of immunoreactive VLDLR proteins with molecular sizes of 143 kDa and 161 kDa. Digestion of the cell extract with the enzymes neuraminidase, N-glycanase, and O-glycanase resulted in the stepwise lowering of the apparent size of the 161-kDa species toward the 143-kDa species. LDLR (-/-) mice fed a 0.2% cholesterol diet were treated with a single intravenous injection of 3 x 10(9) plaque-forming units of AdmVLDLR. Control LDLR (-/-) mice received either phosphate-buffered saline or AdLacZ, a similar adenovirus containing the LacZ cDNA instead of mVLDLR cDNA. Comparison of the plasma lipids in the 3 groups of mice indicates that in the AdmVLDL animals, total cholesterol is reduced by approximately 50% at days 4 and 9 and returned toward control values on day 21. In these animals, there was also a approximately 30% reduction in plasma apolipoprotein (apo) E accompanied by a 90% fall in apoB-100 on day 4 of treatment. By FPLC analysis, the major reduction in plasma cholesterol in the AdmVLDLR animals was accounted for by a marked reduction in the intermediate density lipoprotein/low density lipoprotein (IDL/LDL) fraction. Plasma VLDL, IDL/LDL, and HDL were isolated from the three groups of animals by ultracentrifugal flotation. In the AdmVLDLR animals, there was substantial loss (approximately 65%) of protein and cholesterol mainly in the IDL/LDL fraction on days 4 and 9. Nondenaturing gradient gel electrophoresis indicates a preferential loss of the IDL peak although the LDL peak was also reduced. When 125I-IDL was administered intravenously into animals on day 4, the AdmVLDLR animals cleared the 125I-IDL at a rate 5-10 times higher than the AdLacZ animals. We conclude that adenovirus-mediated transfer of the VLDLR gene induces high-level hepatic expression of the VLDLR and results in a reversal of the hypercholesterolemia in 0.2% cholesterol diet-fed LDLR (-/-, mice. The VLDLR overexpression appears to greatly enhance the ability of these animals to clear IDL, resulting in a marked lowering of the plasma IDL/LDL. Further testing of the use of the VLDLR gene as a therapeutic gene for the treatment of hypercholesterolemia is warranted. | lld:pubmed |
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| pubmed-article:8636110 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:8636110 | pubmed:language | eng | lld:pubmed |
| pubmed-article:8636110 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:8636110 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:8636110 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:8636110 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:8636110 | pubmed:month | Mar | lld:pubmed |
| pubmed-article:8636110 | pubmed:issn | 0021-9258 | lld:pubmed |
| pubmed-article:8636110 | pubmed:author | pubmed-author:KobayashiKK | lld:pubmed |
| pubmed-article:8636110 | pubmed:author | pubmed-author:OkiCC | lld:pubmed |
| pubmed-article:8636110 | pubmed:author | pubmed-author:ChanLL | lld:pubmed |
| pubmed-article:8636110 | pubmed:author | pubmed-author:FortiPP | lld:pubmed |
| pubmed-article:8636110 | pubmed:author | pubmed-author:TenaLL | lld:pubmed |
| pubmed-article:8636110 | pubmed:author | pubmed-author:IshidaBB | lld:pubmed |
| pubmed-article:8636110 | pubmed:author | pubmed-author:NakamutaMM | lld:pubmed |
| pubmed-article:8636110 | pubmed:author | pubmed-author:Ishimura-OkaK... | lld:pubmed |
| pubmed-article:8636110 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:8636110 | pubmed:day | 22 | lld:pubmed |
| pubmed-article:8636110 | pubmed:volume | 271 | lld:pubmed |
| pubmed-article:8636110 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:8636110 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:8636110 | pubmed:pagination | 6852-60 | lld:pubmed |
| pubmed-article:8636110 | pubmed:dateRevised | 2007-11-14 | lld:pubmed |
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| pubmed-article:8636110 | pubmed:year | 1996 | lld:pubmed |
| pubmed-article:8636110 | pubmed:articleTitle | Reversal of hypercholesterolemia in low density lipoprotein receptor knockout mice by adenovirus-mediated gene transfer of the very low density lipoprotein receptor. | lld:pubmed |
| pubmed-article:8636110 | pubmed:affiliation | Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA. | lld:pubmed |
| pubmed-article:8636110 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:8636110 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
| pubmed-article:8636110 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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