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Lysosomal acid lipase deficiency: A rare inherited dyslipidemia but potential ubiquitous factor in the development of atherosclerosis and fatty liver disease

Lysosomal acid lipase (LAL), encoded by the gene LIPA, is the sole neutral lipid hydrolase in lysosomes, responsible for cleavage of cholesteryl esters and triglycerides into their component parts. Inherited forms of complete (Wolman Disease, WD) or partial LAL deficiency (cholesteryl ester storage...

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Autores principales: Besler, Katrina J., Blanchard, Valentin, Francis, Gordon A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9530988/
https://www.ncbi.nlm.nih.gov/pubmed/36204319
http://dx.doi.org/10.3389/fgene.2022.1013266
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author Besler, Katrina J.
Blanchard, Valentin
Francis, Gordon A.
author_facet Besler, Katrina J.
Blanchard, Valentin
Francis, Gordon A.
author_sort Besler, Katrina J.
collection PubMed
description Lysosomal acid lipase (LAL), encoded by the gene LIPA, is the sole neutral lipid hydrolase in lysosomes, responsible for cleavage of cholesteryl esters and triglycerides into their component parts. Inherited forms of complete (Wolman Disease, WD) or partial LAL deficiency (cholesteryl ester storage disease, CESD) are fortunately rare. Recently, LAL has been identified as a cardiovascular risk gene in genome-wide association studies, though the directionality of risk conferred remains controversial. It has also been proposed that the low expression and activity of LAL in arterial smooth muscle cells (SMCs) that occurs inherently in nature is a likely determinant of the propensity of SMCs to form the majority of foam cells in atherosclerotic plaque. LAL also likely plays a potential role in fatty liver disease. This review highlights the nature of LAL gene mutations in WD and CESD, the association of LAL with prediction of cardiovascular risk from genome-wide association studies, the importance of relative LAL deficiency in SMC foam cells, and the need to further interrogate the pathophysiological impact and cell type-specific role of enhancing LAL activity as a novel treatment strategy to reduce the development and induce the regression of ischemic cardiovascular disease and fatty liver.
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spelling pubmed-95309882022-10-05 Lysosomal acid lipase deficiency: A rare inherited dyslipidemia but potential ubiquitous factor in the development of atherosclerosis and fatty liver disease Besler, Katrina J. Blanchard, Valentin Francis, Gordon A. Front Genet Genetics Lysosomal acid lipase (LAL), encoded by the gene LIPA, is the sole neutral lipid hydrolase in lysosomes, responsible for cleavage of cholesteryl esters and triglycerides into their component parts. Inherited forms of complete (Wolman Disease, WD) or partial LAL deficiency (cholesteryl ester storage disease, CESD) are fortunately rare. Recently, LAL has been identified as a cardiovascular risk gene in genome-wide association studies, though the directionality of risk conferred remains controversial. It has also been proposed that the low expression and activity of LAL in arterial smooth muscle cells (SMCs) that occurs inherently in nature is a likely determinant of the propensity of SMCs to form the majority of foam cells in atherosclerotic plaque. LAL also likely plays a potential role in fatty liver disease. This review highlights the nature of LAL gene mutations in WD and CESD, the association of LAL with prediction of cardiovascular risk from genome-wide association studies, the importance of relative LAL deficiency in SMC foam cells, and the need to further interrogate the pathophysiological impact and cell type-specific role of enhancing LAL activity as a novel treatment strategy to reduce the development and induce the regression of ischemic cardiovascular disease and fatty liver. Frontiers Media S.A. 2022-09-20 /pmc/articles/PMC9530988/ /pubmed/36204319 http://dx.doi.org/10.3389/fgene.2022.1013266 Text en Copyright © 2022 Besler, Blanchard and Francis. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Besler, Katrina J.
Blanchard, Valentin
Francis, Gordon A.
Lysosomal acid lipase deficiency: A rare inherited dyslipidemia but potential ubiquitous factor in the development of atherosclerosis and fatty liver disease
title Lysosomal acid lipase deficiency: A rare inherited dyslipidemia but potential ubiquitous factor in the development of atherosclerosis and fatty liver disease
title_full Lysosomal acid lipase deficiency: A rare inherited dyslipidemia but potential ubiquitous factor in the development of atherosclerosis and fatty liver disease
title_fullStr Lysosomal acid lipase deficiency: A rare inherited dyslipidemia but potential ubiquitous factor in the development of atherosclerosis and fatty liver disease
title_full_unstemmed Lysosomal acid lipase deficiency: A rare inherited dyslipidemia but potential ubiquitous factor in the development of atherosclerosis and fatty liver disease
title_short Lysosomal acid lipase deficiency: A rare inherited dyslipidemia but potential ubiquitous factor in the development of atherosclerosis and fatty liver disease
title_sort lysosomal acid lipase deficiency: a rare inherited dyslipidemia but potential ubiquitous factor in the development of atherosclerosis and fatty liver disease
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9530988/
https://www.ncbi.nlm.nih.gov/pubmed/36204319
http://dx.doi.org/10.3389/fgene.2022.1013266
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