Effects of simvastatin on plasma lipoproteins and response to arterial injury in wild-type and apolipoprotein-E-deficient mice.
OBJECTIVE: To test the non-lipid-lowering effects of simvastatin on the response to injury in normolipidemic and hyperlipidemic mice. METHODS AND RESULTS: Wild-type (WT) mice (n = 40) and hyperlipidemic apolipoprotein-E-deficient (apoE(-/-)) mice (n = 40) received normal chow or chow containing sim...
| Huvudupphovsmän: | , , , , , , , , |
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| Materialtyp: | Journal article |
| Språk: | English |
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2004
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| _version_ | 1826288480317079552 |
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| author | Choudhury, R Carrelli, A Stern, J Chereshnev, I Soccio, R Elmalem, V Fallon, J Fisher, E Reis, E |
| author_facet | Choudhury, R Carrelli, A Stern, J Chereshnev, I Soccio, R Elmalem, V Fallon, J Fisher, E Reis, E |
| author_sort | Choudhury, R |
| collection | OXFORD |
| description | OBJECTIVE: To test the non-lipid-lowering effects of simvastatin on the response to injury in normolipidemic and hyperlipidemic mice. METHODS AND RESULTS: Wild-type (WT) mice (n = 40) and hyperlipidemic apolipoprotein-E-deficient (apoE(-/-)) mice (n = 40) received normal chow or chow containing simvastatin 100 mg/kg/day prior to bilateral femoral artery wire injury. Intimal hyperplasia and plasma cholesterol concentration were quantified after 4 weeks. Plasma cholesterol in WT mice treated or untreated with simvastatin was similar (100.9 +/- 6.6 vs. 94.3 +/- 17.5 mg/dl). Simvastatin did not affect intimal hyperplasia. In apoE(-/-) mice, intimal hyperplasia was increased 2.3-fold relative to WT mice (17090 +/- 4998 vs. 39490 +/- 16190; p < 0.001). In apoE(-/- )mice, simvastatin caused a paradoxical increase in plasma cholesterol (1094 +/- 60.3 vs. 658 +/- 66.8 mg/dl; p < 0.001), confirmed by FPLC. This was associated with a further increase in intimal area (39490 +/- 16190 vs. 55420 +/- 22590 mm(2); p < 0.01). CONCLUSIONS: (1). Simvastatin had no effect on plasma cholesterol or the response to arterial injury in normolipidemic WT mice; (2). hyperlipidemia was associated with markedly increased intimal hyperplasia, and (3). simvastatin treatment of apoE(-/-) mice caused paradoxical hyperlipidemia and increased intimal hyperplasia. |
| first_indexed | 2024-03-07T02:14:20Z |
| format | Journal article |
| id | oxford-uuid:a1b55c80-a3a8-410a-91c0-50aa8d1d69d2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T02:14:20Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:a1b55c80-a3a8-410a-91c0-50aa8d1d69d22022-03-27T02:15:06ZEffects of simvastatin on plasma lipoproteins and response to arterial injury in wild-type and apolipoprotein-E-deficient mice.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a1b55c80-a3a8-410a-91c0-50aa8d1d69d2EnglishSymplectic Elements at Oxford2004Choudhury, RCarrelli, AStern, JChereshnev, ISoccio, RElmalem, VFallon, JFisher, EReis, E OBJECTIVE: To test the non-lipid-lowering effects of simvastatin on the response to injury in normolipidemic and hyperlipidemic mice. METHODS AND RESULTS: Wild-type (WT) mice (n = 40) and hyperlipidemic apolipoprotein-E-deficient (apoE(-/-)) mice (n = 40) received normal chow or chow containing simvastatin 100 mg/kg/day prior to bilateral femoral artery wire injury. Intimal hyperplasia and plasma cholesterol concentration were quantified after 4 weeks. Plasma cholesterol in WT mice treated or untreated with simvastatin was similar (100.9 +/- 6.6 vs. 94.3 +/- 17.5 mg/dl). Simvastatin did not affect intimal hyperplasia. In apoE(-/-) mice, intimal hyperplasia was increased 2.3-fold relative to WT mice (17090 +/- 4998 vs. 39490 +/- 16190; p < 0.001). In apoE(-/- )mice, simvastatin caused a paradoxical increase in plasma cholesterol (1094 +/- 60.3 vs. 658 +/- 66.8 mg/dl; p < 0.001), confirmed by FPLC. This was associated with a further increase in intimal area (39490 +/- 16190 vs. 55420 +/- 22590 mm(2); p < 0.01). CONCLUSIONS: (1). Simvastatin had no effect on plasma cholesterol or the response to arterial injury in normolipidemic WT mice; (2). hyperlipidemia was associated with markedly increased intimal hyperplasia, and (3). simvastatin treatment of apoE(-/-) mice caused paradoxical hyperlipidemia and increased intimal hyperplasia. |
| spellingShingle | Choudhury, R Carrelli, A Stern, J Chereshnev, I Soccio, R Elmalem, V Fallon, J Fisher, E Reis, E Effects of simvastatin on plasma lipoproteins and response to arterial injury in wild-type and apolipoprotein-E-deficient mice. |
| title | Effects of simvastatin on plasma lipoproteins and response to arterial injury in wild-type and apolipoprotein-E-deficient mice. |
| title_full | Effects of simvastatin on plasma lipoproteins and response to arterial injury in wild-type and apolipoprotein-E-deficient mice. |
| title_fullStr | Effects of simvastatin on plasma lipoproteins and response to arterial injury in wild-type and apolipoprotein-E-deficient mice. |
| title_full_unstemmed | Effects of simvastatin on plasma lipoproteins and response to arterial injury in wild-type and apolipoprotein-E-deficient mice. |
| title_short | Effects of simvastatin on plasma lipoproteins and response to arterial injury in wild-type and apolipoprotein-E-deficient mice. |
| title_sort | effects of simvastatin on plasma lipoproteins and response to arterial injury in wild type and apolipoprotein e deficient mice |
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