Cargando…
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...
Autores principales: | , , |
---|---|
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 |
_version_ | 1784801805399490560 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9530988 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT beslerkatrinaj lysosomalacidlipasedeficiencyarareinheriteddyslipidemiabutpotentialubiquitousfactorinthedevelopmentofatherosclerosisandfattyliverdisease AT blanchardvalentin lysosomalacidlipasedeficiencyarareinheriteddyslipidemiabutpotentialubiquitousfactorinthedevelopmentofatherosclerosisandfattyliverdisease AT francisgordona lysosomalacidlipasedeficiencyarareinheriteddyslipidemiabutpotentialubiquitousfactorinthedevelopmentofatherosclerosisandfattyliverdisease |