Hypocholesterolemic actions of atorvastatin are associated with alterations on hepatic cholesterol metabolism and lipoprotein composition in the guinea pig
Guinea pigs were fed 15% (w/W) fat, high in lauric and myristic acids, a diet known to produce hypercholesterolemia in these animals. The diet was given alone or in combination with four doses of atorvastatin equivalent to 1, 3, 10, and 20 mg/kg per day. Atorvastatin reduced plasma LDL cholesterol c...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
1996-11-01
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| Series: | Journal of Lipid Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520374861 |
| _version_ | 1818385214474289152 |
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| author | K Conde M Vergara-Jimenez B R Krause R S Newton M L Fernandez |
| author_facet | K Conde M Vergara-Jimenez B R Krause R S Newton M L Fernandez |
| author_sort | K Conde |
| collection | DOAJ |
| description | Guinea pigs were fed 15% (w/W) fat, high in lauric and myristic acids, a diet known to produce hypercholesterolemia in these animals. The diet was given alone or in combination with four doses of atorvastatin equivalent to 1, 3, 10, and 20 mg/kg per day. Atorvastatin reduced plasma LDL cholesterol concentrations by 46, 50, 53, and 70%, respectively (P < 0.001). Plasma apoB concentrations were reduced by atorvastatin (P < 0.001) and compositional changes occurred in VLDL and LDL with reductions of the relative proportion of cholesteryl ester and increases in triacylglycerol. A reduction in hepatic cholesteryl ester (66%) was observed only with the highest atorvastatin dose (20 mg/kg per day) while microsomal cholesterol was reduced by 30% with 3-20 mg/kg per day. Hepatic ACAT activity was down-regulated and apoB/E receptor number was increased by atorvastatin. In contrast, HMG-CoA reductase activity and cholesterol 7 alpha-hydroxylase were not affected by the drug. VLDL apoB secretion rates were decreased by atorvastatin treatment 59 and 76% with 3 and 20 mg/kg per day, respectively. Nascent VLDL particles were larger after drug treatment, showing an increased number in triacylglycerol molecules. These results support the hypothesis that the plasma LDL lowering induced by atorvastatin is due to a decreased secretion of apoB in combination with an increase of hepatic apoB/E receptors. |
| first_indexed | 2024-12-14T03:34:36Z |
| format | Article |
| id | doaj.art-efee5b67c61547419ca29a5ea8ee3e33 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-14T03:34:36Z |
| publishDate | 1996-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-efee5b67c61547419ca29a5ea8ee3e332022-12-21T23:18:39ZengElsevierJournal of Lipid Research0022-22751996-11-01371123722382Hypocholesterolemic actions of atorvastatin are associated with alterations on hepatic cholesterol metabolism and lipoprotein composition in the guinea pigK Conde0M Vergara-Jimenez1B R Krause2R S Newton3M L Fernandez4Department of Nutritional Sciences, University of Arizona, Tucson 85721, USA.Department of Nutritional Sciences, University of Arizona, Tucson 85721, USA.Department of Nutritional Sciences, University of Arizona, Tucson 85721, USA.Department of Nutritional Sciences, University of Arizona, Tucson 85721, USA.Department of Nutritional Sciences, University of Arizona, Tucson 85721, USA.Guinea pigs were fed 15% (w/W) fat, high in lauric and myristic acids, a diet known to produce hypercholesterolemia in these animals. The diet was given alone or in combination with four doses of atorvastatin equivalent to 1, 3, 10, and 20 mg/kg per day. Atorvastatin reduced plasma LDL cholesterol concentrations by 46, 50, 53, and 70%, respectively (P < 0.001). Plasma apoB concentrations were reduced by atorvastatin (P < 0.001) and compositional changes occurred in VLDL and LDL with reductions of the relative proportion of cholesteryl ester and increases in triacylglycerol. A reduction in hepatic cholesteryl ester (66%) was observed only with the highest atorvastatin dose (20 mg/kg per day) while microsomal cholesterol was reduced by 30% with 3-20 mg/kg per day. Hepatic ACAT activity was down-regulated and apoB/E receptor number was increased by atorvastatin. In contrast, HMG-CoA reductase activity and cholesterol 7 alpha-hydroxylase were not affected by the drug. VLDL apoB secretion rates were decreased by atorvastatin treatment 59 and 76% with 3 and 20 mg/kg per day, respectively. Nascent VLDL particles were larger after drug treatment, showing an increased number in triacylglycerol molecules. These results support the hypothesis that the plasma LDL lowering induced by atorvastatin is due to a decreased secretion of apoB in combination with an increase of hepatic apoB/E receptors.http://www.sciencedirect.com/science/article/pii/S0022227520374861 |
| spellingShingle | K Conde M Vergara-Jimenez B R Krause R S Newton M L Fernandez Hypocholesterolemic actions of atorvastatin are associated with alterations on hepatic cholesterol metabolism and lipoprotein composition in the guinea pig Journal of Lipid Research |
| title | Hypocholesterolemic actions of atorvastatin are associated with alterations on hepatic cholesterol metabolism and lipoprotein composition in the guinea pig |
| title_full | Hypocholesterolemic actions of atorvastatin are associated with alterations on hepatic cholesterol metabolism and lipoprotein composition in the guinea pig |
| title_fullStr | Hypocholesterolemic actions of atorvastatin are associated with alterations on hepatic cholesterol metabolism and lipoprotein composition in the guinea pig |
| title_full_unstemmed | Hypocholesterolemic actions of atorvastatin are associated with alterations on hepatic cholesterol metabolism and lipoprotein composition in the guinea pig |
| title_short | Hypocholesterolemic actions of atorvastatin are associated with alterations on hepatic cholesterol metabolism and lipoprotein composition in the guinea pig |
| title_sort | hypocholesterolemic actions of atorvastatin are associated with alterations on hepatic cholesterol metabolism and lipoprotein composition in the guinea pig |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520374861 |
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