Genetics and regulation of HDL metabolism.

Abstract

The inverse association between plasma HDL cholesterol (HDL-C) levels and risk for cardiovascular disease (CVD) has been demonstrated by numerous epidemiological studies. However, efforts to reduce CVD risk by pharmaceutically manipulating HDL-C levels failed and refused the HDL hypothesis. HDL-C levels in the general population are highly heterogeneous and are determined by a combination of genetic and environmental factors. Insights into the causes of HDL-C heterogeneity came from the study of monogenic HDL deficiency syndromes but also from genome wide association and Μendelian randomization studies which revealed the contribution of a large number of loci to low or high HDL-C cases in the general or in restricted ethnic populations. Furthermore, HDL-C levels in the plasma are under the control of transcription factor families acting primarily in the liver including members of the hormone nuclear receptors (PPARs, LXRs, HNF-4) and forkhead box proteins (FOXO1-4) and activating transcription factors (ATFs). The effects of certain lipid lowering drugs used today are based on the modulation of the activity of specific members of these transcription factors. During the past decade, the roles of small or long non-coding RNAs acting post-transcriptionally on the expression of HDL genes have emerged and provided novel insights into HDL regulation and new opportunities for therapeutic interventions. In the present review we summarize recent progress made in the genetics and the regulation (transcriptional and post-transcriptional) of HDL metabolism.

• Authors: Dimitris Kardassis, Efstathia Thymiakou, Angeliki Chroni
• Journal: Biochimica et biophysica acta. Molecular and cell biology of lipids (Biochim Biophys Acta Mol Cell Biol Lipids) Vol. 1867 Issue 1 Pg. 159060 (01 2022) ISSN: 1879-2618 [Electronic] Netherlands
• PMID: 34624513 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

Chemical References

• Activating Transcription Factors
• Cholesterol, HDL
• Forkhead Transcription Factors
• Lipoproteins, HDL
• RNA, Long Noncoding
• Receptors, Cytoplasmic and Nuclear

Topics

• Activating Transcription Factors (blood, genetics)
• Cholesterol, HDL (blood, genetics, metabolism)
• Forkhead Transcription Factors (blood, genetics)
• Genetic Heterogeneity
• Heart Disease Risk Factors
• Humans
• Lipoproteins, HDL (blood, genetics, metabolism)
• Liver (metabolism, pathology)
• RNA, Long Noncoding (blood, genetics)
• Receptors, Cytoplasmic and Nuclear (blood, genetics)