Cited 39 times in
Up-regulation of hepatic low-density lipoprotein receptor-related protein 1: a possible novel mechanism of antiatherogenic activity of hydroxymethylglutaryl-coenzyme A reductase inhibitor Atorvastatin and hepatic LRP1 expression
DC Field | Value | Language |
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dc.contributor.author | 강샛별 | - |
dc.contributor.author | 강은석 | - |
dc.contributor.author | 문재훈 | - |
dc.contributor.author | 박종숙 | - |
dc.contributor.author | 안철우 | - |
dc.contributor.author | 이병완 | - |
dc.contributor.author | 이현철 | - |
dc.contributor.author | 차봉수 | - |
dc.date.accessioned | 2014-12-20T16:58:54Z | - |
dc.date.available | 2014-12-20T16:58:54Z | - |
dc.date.issued | 2011 | - |
dc.identifier.issn | 0026-0495 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/93744 | - |
dc.description.abstract | Low-density lipoprotein receptor-related protein 1 (LRP1) binds to apolipoprotein E and serves as a receptor for remnant lipoproteins in the liver, thus playing an important role in clearing these atherogenic particles. In this study, we investigated the effect of atorvastatin, a hydroxymethylglutaryl-coenzyme A reductase inhibitor, on hepatic LRP1 expression. We used HepG2 and Hep3B cells for in vitro study, and Otsuka Long-Evans Tokushima fatty and Sprague-Dawley rats for in vivo study. We used relatively high pharmacologic dose of atorvastatin in this study (in vitro, 0.5 μmol/L in culture media, for 48 hours; in vivo, 20 mg/[kg d], for 6 weeks). Atorvastatin increased LRP1 and low-density lipoprotein (LDL) receptor expression in HepG2 and Hep3B cells and induced hepatic LRP1 and LDL receptor expression in chow diet-fed Sprague-Dawley rats and high-fat diet-fed Otsuka Long-Evans Tokushima fatty rats. Atorvastatin decreased intracellular sterol level and increased the amount of the nuclear form of sterol response element-binding protein-2 (SREBP-2) in both HepG2 and Hep3B cells as well as in two animal models. Treatment of HepG2 cells with LDL increased intracellular sterol level and reduced LRP1, LDL receptor, and SREBP-2. When SREBP-2 in HepG2 cells was knocked down by small interfering RNA, the induction of LRP1 expression by atorvastatin did not take place. In conclusion, up-regulation of hepatic LRP1 might be a novel mechanism by which statin treatment decreases remnant lipoproteins. In addition, SREBP-2 acts as a mediator of atorvastatin-induced up-regulation of hepatic LRP1. Future studies using standard doses of atorvastatin in humans are needed to elucidate clinical relevance of these findings. | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 930~940 | - |
dc.relation.isPartOf | METABOLISM-CLINICAL AND EXPERIMENTAL | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Antigens, CD/biosynthesis* | - |
dc.subject.MESH | Atherosclerosis/etiology | - |
dc.subject.MESH | Atherosclerosis/metabolism* | - |
dc.subject.MESH | Atorvastatin Calcium | - |
dc.subject.MESH | Dietary Fats/adverse effects | - |
dc.subject.MESH | Hep G2 Cells | - |
dc.subject.MESH | Heptanoic Acids/pharmacology* | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology* | - |
dc.subject.MESH | Lipoproteins, LDL/pharmacology | - |
dc.subject.MESH | Liver/drug effects* | - |
dc.subject.MESH | Liver/metabolism | - |
dc.subject.MESH | Low Density Lipoprotein Receptor-Related Protein-1/biosynthesis* | - |
dc.subject.MESH | Pyrroles/pharmacology* | - |
dc.subject.MESH | RNA, Small Interfering/genetics | - |
dc.subject.MESH | Rats | - |
dc.subject.MESH | Rats, Long-Evans | - |
dc.subject.MESH | Rats, Sprague-Dawley | - |
dc.subject.MESH | Sterol Regulatory Element Binding Protein 2/metabolism | - |
dc.subject.MESH | Sterol Regulatory Element Binding Proteins/metabolism | - |
dc.subject.MESH | Up-Regulation | - |
dc.title | Up-regulation of hepatic low-density lipoprotein receptor-related protein 1: a possible novel mechanism of antiatherogenic activity of hydroxymethylglutaryl-coenzyme A reductase inhibitor Atorvastatin and hepatic LRP1 expression | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Medical Research Center (임상의학연구센터) | - |
dc.contributor.googleauthor | Jae Hoon Moon | - |
dc.contributor.googleauthor | Saet Byol Kang | - |
dc.contributor.googleauthor | Jong Suk Park | - |
dc.contributor.googleauthor | Byung Wan Lee | - |
dc.contributor.googleauthor | Eun Seok Kang | - |
dc.contributor.googleauthor | Chul Woo Ahn | - |
dc.contributor.googleauthor | Hyun Chul Lee | - |
dc.contributor.googleauthor | Bong Soo Cha | - |
dc.identifier.doi | 10.1016/j.metabol.2010.08.013 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A00035 | - |
dc.contributor.localId | A00068 | - |
dc.contributor.localId | A01378 | - |
dc.contributor.localId | A02270 | - |
dc.contributor.localId | A02796 | - |
dc.contributor.localId | A03301 | - |
dc.contributor.localId | A03996 | - |
dc.contributor.localId | A01660 | - |
dc.relation.journalcode | J02223 | - |
dc.identifier.eissn | 1532-8600 | - |
dc.identifier.pmid | 20951395 | - |
dc.identifier.url | http://www.sciencedirect.com/science/article/pii/S002604951000301X | - |
dc.contributor.alternativeName | Kang, Saet Byol | - |
dc.contributor.alternativeName | Kang, Eun Seok | - |
dc.contributor.alternativeName | Moon, Jae Hoon | - |
dc.contributor.alternativeName | Park, Jong Suk | - |
dc.contributor.alternativeName | Ahn, Chul Woo | - |
dc.contributor.alternativeName | Lee, Byung Wan | - |
dc.contributor.alternativeName | Lee, Hyun Chul | - |
dc.contributor.alternativeName | Cha, Bong Soo | - |
dc.contributor.affiliatedAuthor | Kang, Saet Byol | - |
dc.contributor.affiliatedAuthor | Kang, Eun Seok | - |
dc.contributor.affiliatedAuthor | Moon, Jae Hoon | - |
dc.contributor.affiliatedAuthor | Ahn, Chul Woo | - |
dc.contributor.affiliatedAuthor | Lee, Byung Wan | - |
dc.contributor.affiliatedAuthor | Lee, Hyun Chul | - |
dc.contributor.affiliatedAuthor | Cha, Bong Soo | - |
dc.contributor.affiliatedAuthor | Park, Jong Suk | - |
dc.rights.accessRights | not free | - |
dc.citation.volume | 60 | - |
dc.citation.number | 7 | - |
dc.citation.startPage | 930 | - |
dc.citation.endPage | 940 | - |
dc.identifier.bibliographicCitation | METABOLISM-CLINICAL AND EXPERIMENTAL, Vol.60(7) : 930-940, 2011 | - |
dc.identifier.rimsid | 28431 | - |
dc.type.rims | ART | - |
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