Cargando…

Sphingolipids in Atherosclerosis: Chimeras in Structure and Function

Atherosclerosis—a systemic inflammatory disease—is the number one cause of mortality and morbidity worldwide. As such, the prevention of disease progression is of global interest in order to reduce annual deaths at a significant scale. Atherosclerosis is characterized by plaque formation in the arte...

Descripción completa

Detalles Bibliográficos
Autores principales: Peters, Lisa, Kuebler, Wolfgang M., Simmons, Szandor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570378/
https://www.ncbi.nlm.nih.gov/pubmed/36233252
http://dx.doi.org/10.3390/ijms231911948
_version_ 1784810091488215040
author Peters, Lisa
Kuebler, Wolfgang M.
Simmons, Szandor
author_facet Peters, Lisa
Kuebler, Wolfgang M.
Simmons, Szandor
author_sort Peters, Lisa
collection PubMed
description Atherosclerosis—a systemic inflammatory disease—is the number one cause of mortality and morbidity worldwide. As such, the prevention of disease progression is of global interest in order to reduce annual deaths at a significant scale. Atherosclerosis is characterized by plaque formation in the arteries, resulting in vascular events such as ischemic stroke or myocardial infarction. A better understanding of the underlying pathophysiological processes at the cellular and molecular level is indispensable to identify novel therapeutic targets that may alleviate disease initiation or progression. Sphingolipids—a lipid class named after the chimeric creature sphinx—are considered to play a critical and, metaphorically, equally chimeric regulatory role in atherogenesis. Previous studies identified six common sphingolipids, namely dihydroceramide (DhCer), ceramide (Cer), sphingosine-1-phosphate (S1P), sphingomyelin (SM), lactosylceramide (LacCer), and glucosylceramide (GluCer) in carotid plaques, and demonstrated their potential as inducers of plaque inflammation. In this review, we point out their specific roles in atherosclerosis by focusing on different cell types, carrier molecules, enzymes, and receptors involved in atherogenesis. Whereas we assume mainly atheroprotective effects for GluCer and LacCer, the sphingolipids DhCer, Cer, SM and S1P mediate chimeric functions. Initial studies demonstrate the successful use of interventions in the sphingolipid pathway to prevent atherosclerosis. However, as atherosclerosis is a multifactorial disease with a variety of underlying cellular processes, it is imperative for future research to emphasize the circumstances in which sphingolipids exert protective or progressive functions and to evaluate their therapeutic benefits in a spatiotemporal manner.
format Online
Article
Text
id pubmed-9570378
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-95703782022-10-17 Sphingolipids in Atherosclerosis: Chimeras in Structure and Function Peters, Lisa Kuebler, Wolfgang M. Simmons, Szandor Int J Mol Sci Review Atherosclerosis—a systemic inflammatory disease—is the number one cause of mortality and morbidity worldwide. As such, the prevention of disease progression is of global interest in order to reduce annual deaths at a significant scale. Atherosclerosis is characterized by plaque formation in the arteries, resulting in vascular events such as ischemic stroke or myocardial infarction. A better understanding of the underlying pathophysiological processes at the cellular and molecular level is indispensable to identify novel therapeutic targets that may alleviate disease initiation or progression. Sphingolipids—a lipid class named after the chimeric creature sphinx—are considered to play a critical and, metaphorically, equally chimeric regulatory role in atherogenesis. Previous studies identified six common sphingolipids, namely dihydroceramide (DhCer), ceramide (Cer), sphingosine-1-phosphate (S1P), sphingomyelin (SM), lactosylceramide (LacCer), and glucosylceramide (GluCer) in carotid plaques, and demonstrated their potential as inducers of plaque inflammation. In this review, we point out their specific roles in atherosclerosis by focusing on different cell types, carrier molecules, enzymes, and receptors involved in atherogenesis. Whereas we assume mainly atheroprotective effects for GluCer and LacCer, the sphingolipids DhCer, Cer, SM and S1P mediate chimeric functions. Initial studies demonstrate the successful use of interventions in the sphingolipid pathway to prevent atherosclerosis. However, as atherosclerosis is a multifactorial disease with a variety of underlying cellular processes, it is imperative for future research to emphasize the circumstances in which sphingolipids exert protective or progressive functions and to evaluate their therapeutic benefits in a spatiotemporal manner. MDPI 2022-10-08 /pmc/articles/PMC9570378/ /pubmed/36233252 http://dx.doi.org/10.3390/ijms231911948 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Peters, Lisa
Kuebler, Wolfgang M.
Simmons, Szandor
Sphingolipids in Atherosclerosis: Chimeras in Structure and Function
title Sphingolipids in Atherosclerosis: Chimeras in Structure and Function
title_full Sphingolipids in Atherosclerosis: Chimeras in Structure and Function
title_fullStr Sphingolipids in Atherosclerosis: Chimeras in Structure and Function
title_full_unstemmed Sphingolipids in Atherosclerosis: Chimeras in Structure and Function
title_short Sphingolipids in Atherosclerosis: Chimeras in Structure and Function
title_sort sphingolipids in atherosclerosis: chimeras in structure and function
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570378/
https://www.ncbi.nlm.nih.gov/pubmed/36233252
http://dx.doi.org/10.3390/ijms231911948
work_keys_str_mv AT peterslisa sphingolipidsinatherosclerosischimerasinstructureandfunction
AT kueblerwolfgangm sphingolipidsinatherosclerosischimerasinstructureandfunction
AT simmonsszandor sphingolipidsinatherosclerosischimerasinstructureandfunction