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Gene Expression in Atherosclerotic Lesion of ApoE Deficient Mice

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Abstract

Background

Atherosclerosis, the major cause of mortality and invalidity in industrialized countries, is a multi-factorial disease associated with high plasma cholesterol levels and inflammation in the vessel wall. Many different genes have previously been demonstrated in atherosclerosis, although limited numbers of genes are dealt with in each study. In general, data on dynamic gene expression during disease progress is limited and large-scale evaluation of gene expression patterns during atherogenesis could lead to a better understanding of the key events in the pathogenesis of atherosclerosis. We have therefore applied a mouse gene filter array to analyze gene expression in atherosclerotic ApoE-deficient mice.

Materials and Methods

ApoE-deficient mice were fed atherogenic western diet for 10 or 20 weeks and aortas isolated. C57BL/6 mice on normal chow were used as controls. The mRNAs of 15 animals were pooled and hybridized onto commercially available Clontech mouse gene array filters.

Results

The overall gene expression in the ApoE-deficient and control mice correlated well at both time points. Gene expression profiling showed varying patterns including genes up-regulated at 10 or 20 weeks only. At 20 weeks of diet, an increasing number of up-regulated genes were found in ApoE-deficient mice.

Conclusions

The gene expression in atherogenesis is not a linear process with a maximal expression at advanced lesion stage. Instead, several genes demonstrate a dynamic expression pattern with peaks at the intermediate lesions stage. Thus, detailed evaluation of gene expression at several time points should help understanding the development of atherosclerosis and establishment of preventive intervention.

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Acknowledgments

We are greatly in debt to Inger Bodin for technical assistance. This project was supported by grants from the Swedish Medical Research Council (12660), the Swedish Heart-Lung Foundation, the Torsten and Ragnar Söderberg Foundation, the Åke Wiberg Foundation, the Magnus Bergvall Foundation, the Foundation for Old Servants, and the Professor Nanna Svartz Foundation.

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Authors and Affiliations

  1. Cardiovascular Research Unit, Center for Molecular Medicine, Department of Medicine, L8:03, Karolinska Hospital, S-171 76, Stockholm, Sweden

    Dirk Marcus Wuttge, Allan Sirsjö & Sten Stemme

  2. Department of Medicine, Karolinska Hospital, King Gustaf V Research Institute, Stockholm, Sweden

    Per Eriksson

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  1. Dirk Marcus Wuttge
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  2. Allan Sirsjö
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  4. Sten Stemme
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Correspondence to Sten Stemme.

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Contributed by H. Wigzell.

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Wuttge, D.M., Sirsjö, A., Eriksson, P. et al. Gene Expression in Atherosclerotic Lesion of ApoE Deficient Mice. Mol Med 7, 383–392 (2001). https://doi.org/10.1007/BF03402184

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