Miranda Van Eck1. 1. Division of Biopharmaceutics, Cluster BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, The Netherlands.
Abstract
PURPOSE OF REVIEW: ATP-binding cassette transporter A1 (ABCA1) facilitates cellular cholesterol efflux to lipid-poor apolipoprotein AI (apoAI) and plays a key role in the formation and function of HDL. This review summarizes the advances and new insights in the role of ABCA1 in cardiovascular and metabolic diseases from studies in genetically engineered mice. RECENT FINDINGS: Recent studies show that low HDL associated with liver-specific deletion of ABCA1 does not affect macrophage reverse cholesterol transport or atherosclerosis susceptibility. In the intestine, ABCA1 contributes to the packaging of dietary cholesterol into HDL. Locally in the arterial wall, ABCA1 influences atherosclerosis by acting not only in bone marrow-derived cells but also in endothelial cells and smooth muscle cells. Furthermore, other than its established role in regulating insulin secretion by β-cells, evidence is provided that adipocyte-specific ABCA1 prevents fat storage and the development of impaired glucose tolerance. Moreover, new insights are provided on the post-transcriptional regulation of ABCA1 expression by microRNAs. SUMMARY: Recent studies underscore the importance of ABCA1 in the prevention of cardiovascular and metabolic diseases. Furthermore, the discovery of the extensive regulation of ABCA1 expression by microRNAs has unraveled novel therapeutic targets for ABCA1-based strategies for the treatment of these diseases.
PURPOSE OF REVIEW: ATP-binding cassette transporter A1 (ABCA1) facilitates cellular cholesterol efflux to lipid-poor apolipoprotein AI (apoAI) and plays a key role in the formation and function of HDL. This review summarizes the advances and new insights in the role of ABCA1 in cardiovascular and metabolic diseases from studies in genetically engineered mice. RECENT FINDINGS: Recent studies show that low HDL associated with liver-specific deletion of ABCA1 does not affect macrophage reverse cholesterol transport or atherosclerosis susceptibility. In the intestine, ABCA1 contributes to the packaging of dietary cholesterol into HDL. Locally in the arterial wall, ABCA1 influences atherosclerosis by acting not only in bone marrow-derived cells but also in endothelial cells and smooth muscle cells. Furthermore, other than its established role in regulating insulin secretion by β-cells, evidence is provided that adipocyte-specific ABCA1 prevents fat storage and the development of impaired glucose tolerance. Moreover, new insights are provided on the post-transcriptional regulation of ABCA1 expression by microRNAs. SUMMARY: Recent studies underscore the importance of ABCA1 in the prevention of cardiovascular and metabolic diseases. Furthermore, the discovery of the extensive regulation of ABCA1 expression by microRNAs has unraveled novel therapeutic targets for ABCA1-based strategies for the treatment of these diseases.
Authors: Kai Yin; Yong You; Vicki Swier; Lin Tang; Mohamed M Radwan; Amit N Pandya; Devendra K Agrawal Journal: Arterioscler Thromb Vasc Biol Date: 2015-09-17 Impact factor: 8.311