Metabolism of HDL and its Regulation

Author(s): D. Kardassis, I. Mosialou, M. Kanaki, I. Tiniakou, E. Thymiakou

Journal Name: Current Medicinal Chemistry

Volume 21 , Issue 25 , 2014

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Epidemiological studies have shown that low plasma levels of High Density Lipoprotein Cholesterol (HDL-C) are associated with an increased risk for myocardial infarction. These studies suggested that by increasing HDL-C levels one could reduce cardiovascular risk. However, emerging evidence from studies in animals and humans indicate that high levels of HDL-C are not sufficient to confer atheroprotection but that the functionality of the HDL particles is equally important. The picture is complicated further by the finding that HDL functionality is compromised in patients with chronic inflammatory diseases such as Coronary Artery Disease (CAD), diabetes and rheumatoid arthritis. Despite these obstacles, HDL raising is still a promising strategy for the reduction of CAD risk. Low HDL-C can be caused by inactivating mutations in apoA-I, ATP Binding Cassette Transporter A1 (ABCA1) or Lecithin-Cholesterol Acyl Transferase (LCAT) which affect HDL biogenesis and maturation whereas high HDL-C can be caused by mutations in Cholesteryl Ester Transfer Protein (CETP) or Scavenger receptor Class B Type I (SR-BI). Recent studies suggest that heterogeneity in HDL levels in the population is polygenic in origin. One approach to raise plasma HDL-C is to increase the rate of HDL biosynthesis by capitalizing on the mechanisms that control the transcription of genes that play key roles in HDL biogenesis. We review some of the genetic and non-genetic factors that affect plasma HDL levels and functions and discuss the mechanisms that regulate HDL metabolism at the level of gene transcription in the liver focusing on apoA-I, ABCA1 and apoM.

Keywords: ABCA1, apoA-I, apoM, atherosclerosis, gene transcription, HDL, HDL-based therapies, hepatocyte nuclear factors, hormone nuclear receptors.

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Article Details

Year: 2014
Published on: 24 July, 2014
Page: [2864 - 2880]
Pages: 17
DOI: 10.2174/0929867321666140303153430
Price: $65

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