Atherosclerosis in aged mice over-expressing the reverse cholesterol transport genes
We determined whether over-expression of one of the three genes involved in reverse cholesterol transport, apolipoprotein (apo) AI, lecithin-cholesterol acyl transferase (LCAT) and cholesteryl ester transfer protein (CETP), or of their combinations influenced the development of diet-induced atherosc...
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| Format: | Article |
| Language: | English |
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Associação Brasileira de Divulgação Científica
2005-03-01
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| Series: | Brazilian Journal of Medical and Biological Research |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2005000300010 |
| _version_ | 1819100637666738176 |
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| author | J.A. Berti E.C. de Faria H.C.F. Oliveira |
| author_facet | J.A. Berti E.C. de Faria H.C.F. Oliveira |
| author_sort | J.A. Berti |
| collection | DOAJ |
| description | We determined whether over-expression of one of the three genes involved in reverse cholesterol transport, apolipoprotein (apo) AI, lecithin-cholesterol acyl transferase (LCAT) and cholesteryl ester transfer protein (CETP), or of their combinations influenced the development of diet-induced atherosclerosis. Eight genotypic groups of mice were studied (AI, LCAT, CETP, LCAT/AI, CETP/AI, LCAT/CETP, LCAT/AI/CETP, and non-transgenic) after four months on an atherogenic diet. The extent of atherosclerosis was assessed by morphometric analysis of lipid-stained areas in the aortic roots. The relative influence (R²) of genotype, sex, total cholesterol, and its main sub-fraction levels on atherosclerotic lesion size was determined by multiple linear regression analysis. Whereas apo AI (R² = 0.22, P < 0.001) and CETP (R² = 0.13, P < 0.01) expression reduced lesion size, the LCAT (R² = 0.16, P < 0.005) and LCAT/AI (R² = 0.13, P < 0.003) genotypes had the opposite effect. Logistic regression analysis revealed that the risk of developing atherosclerotic lesions greater than the 50th percentile was 4.3-fold lower for the apo AI transgenic mice than for non-transgenic mice, and was 3.0-fold lower for male than for female mice. These results show that apo AI overexpression decreased the risk of developing large atherosclerotic lesions but was not sufficient to reduce the atherogenic effect of LCAT when both transgenes were co-expressed. On the other hand, CETP expression was sufficient to eliminate the deleterious effect of LCAT and LCAT/AI overexpression. Therefore, increasing each step of the reverse cholesterol transport per se does not necessarily imply protection against atherosclerosis while CETP expression can change specific athero genic scenarios. |
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| format | Article |
| id | doaj.art-f407a67c24994d3198820a3287f43847 |
| institution | Directory Open Access Journal |
| issn | 0100-879X 1414-431X |
| language | English |
| last_indexed | 2024-12-22T01:05:57Z |
| publishDate | 2005-03-01 |
| publisher | Associação Brasileira de Divulgação Científica |
| record_format | Article |
| series | Brazilian Journal of Medical and Biological Research |
| spelling | doaj.art-f407a67c24994d3198820a3287f438472022-12-21T18:44:06ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research0100-879X1414-431X2005-03-0138339139810.1590/S0100-879X2005000300010Atherosclerosis in aged mice over-expressing the reverse cholesterol transport genesJ.A. BertiE.C. de FariaH.C.F. OliveiraWe determined whether over-expression of one of the three genes involved in reverse cholesterol transport, apolipoprotein (apo) AI, lecithin-cholesterol acyl transferase (LCAT) and cholesteryl ester transfer protein (CETP), or of their combinations influenced the development of diet-induced atherosclerosis. Eight genotypic groups of mice were studied (AI, LCAT, CETP, LCAT/AI, CETP/AI, LCAT/CETP, LCAT/AI/CETP, and non-transgenic) after four months on an atherogenic diet. The extent of atherosclerosis was assessed by morphometric analysis of lipid-stained areas in the aortic roots. The relative influence (R²) of genotype, sex, total cholesterol, and its main sub-fraction levels on atherosclerotic lesion size was determined by multiple linear regression analysis. Whereas apo AI (R² = 0.22, P < 0.001) and CETP (R² = 0.13, P < 0.01) expression reduced lesion size, the LCAT (R² = 0.16, P < 0.005) and LCAT/AI (R² = 0.13, P < 0.003) genotypes had the opposite effect. Logistic regression analysis revealed that the risk of developing atherosclerotic lesions greater than the 50th percentile was 4.3-fold lower for the apo AI transgenic mice than for non-transgenic mice, and was 3.0-fold lower for male than for female mice. These results show that apo AI overexpression decreased the risk of developing large atherosclerotic lesions but was not sufficient to reduce the atherogenic effect of LCAT when both transgenes were co-expressed. On the other hand, CETP expression was sufficient to eliminate the deleterious effect of LCAT and LCAT/AI overexpression. Therefore, increasing each step of the reverse cholesterol transport per se does not necessarily imply protection against atherosclerosis while CETP expression can change specific athero genic scenarios.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2005000300010Apolipoprotein AICholesteryl ester transfer proteinLecithin-cholesterol acyl transferaseAtherosclerosisTransgenic mice |
| spellingShingle | J.A. Berti E.C. de Faria H.C.F. Oliveira Atherosclerosis in aged mice over-expressing the reverse cholesterol transport genes Brazilian Journal of Medical and Biological Research Apolipoprotein AI Cholesteryl ester transfer protein Lecithin-cholesterol acyl transferase Atherosclerosis Transgenic mice |
| title | Atherosclerosis in aged mice over-expressing the reverse cholesterol transport genes |
| title_full | Atherosclerosis in aged mice over-expressing the reverse cholesterol transport genes |
| title_fullStr | Atherosclerosis in aged mice over-expressing the reverse cholesterol transport genes |
| title_full_unstemmed | Atherosclerosis in aged mice over-expressing the reverse cholesterol transport genes |
| title_short | Atherosclerosis in aged mice over-expressing the reverse cholesterol transport genes |
| title_sort | atherosclerosis in aged mice over expressing the reverse cholesterol transport genes |
| topic | Apolipoprotein AI Cholesteryl ester transfer protein Lecithin-cholesterol acyl transferase Atherosclerosis Transgenic mice |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2005000300010 |
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