Metabolism of HDL and its Regulation

Title:Metabolism of HDL and its Regulation

Volume: 21 Issue: 25

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

Affiliation:

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

Abstract: 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.

Cite this article as:

Kardassis D., Mosialou I., Kanaki M., Tiniakou I. and Thymiakou E., Metabolism of HDL and its Regulation, Current Medicinal Chemistry 2014; 21 (25) . https://dx.doi.org/10.2174/0929867321666140303153430