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Therapeutic Interventions to Enhance Apolipoprotein A-I-Mediated Cardioprotection

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Abstract

The principal function of high-density lipoprotein (HDL) is to facilitate the reverse cholesterol transport (RCT) and inhibition of atheroma formation. Epidemiological studies and interventional trials have suggested that HDL has cardioprotective properties. However, increasing HDL concentration may not necessarily increase RCT, especially if the increase in HDL levels is the result of inhibiting HDL cholesterol (HDL-C) flux. The results of recent phase III clinical trials utilizing a cholesterol ester transfer protein (CETP) inhibitor to increase HDL-C levels in hypoalphalipoproteinaemia have shown that this approach of elevating HDL-C levels is insufficient to combat atherosclerosis and reduce the risk of cardiovascular disease. Although there are several interventions that increase HDL-C by preventing its turnover in the circulation, a more desirable approach is to enhance de novo production of HDL in the liver and/or small intestine. To this end, our acquired knowledge of the apolipoprotein-I (apo A-I) gene promoter as well as the signalling pathways that modulate its expression, has fuelled the development of novel therapeutic strategies to increase HDL-C flux. Promising pharmacological agents that selectively regulate transcription of the apo A-I gene, therapeutic strategies to de-repress apo A-I gene expression, and infusion of recombinant apo A-I or apo A-I mimetics are under development and may be clinically beneficial in the near future.

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Acknowledgements

This work is supported by the University of Florida — Jacksonville College of Medicine research grant to Michael Haas. The authors declare that no conflicts of interest exist that prejudice the impartiality of this review article, and that there are no financial or other conflicts of interest associated with the manuscript.

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  1. Department of Medicine, University of Florida College of Medicine, 653-1 West Eighth Street, L14, Jacksonville, Florida, 32209, USA

    Michael J. Haas & Arshag D. Mooradian

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  1. Michael J. Haas
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  2. Arshag D. Mooradian
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Correspondence to Michael J. Haas.

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Haas, M.J., Mooradian, A.D. Therapeutic Interventions to Enhance Apolipoprotein A-I-Mediated Cardioprotection. Drugs 70, 805–821 (2010). https://doi.org/10.2165/11535410-000000000-00000

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