Cholesterol lowering depletes atherosclerotic lesions of smooth muscle cell-derived fibromyocytes and chondromyocytes.
Animals
Plaque, Atherosclerotic
/ pathology
Myocytes, Smooth Muscle
/ drug effects
Atherosclerosis
/ pathology
Disease Models, Animal
Chondrocytes
/ drug effects
Signal Transduction
/ drug effects
Mice, Inbred C57BL
Anticholesteremic Agents
/ pharmacology
Male
Cholesterol
/ metabolism
Mice
Aortic Diseases
/ pathology
Single-Cell Analysis
Muscle, Smooth, Vascular
/ drug effects
NF-kappa B
/ metabolism
Journal
Nature cardiovascular research
ISSN: 2731-0590
Titre abrégé: Nat Cardiovasc Res
Pays: England
ID NLM: 9918284280206676
Informations de publication
Date de publication:
Feb 2024
Feb 2024
Historique:
received:
03
08
2022
accepted:
14
12
2023
medline:
28
8
2024
pubmed:
28
8
2024
entrez:
28
8
2024
Statut:
ppublish
Résumé
Drugs that lower plasma apolipoprotein B (ApoB)-containing lipoproteins are central to treating advanced atherosclerosis and provide partial protection against clinical events. Previous research showed that lowering ApoB-containing lipoproteins stops plaque inflammation, but how these drugs affect the heterogeneous population of plaque cells derived from smooth muscle cells (SMCs) is unknown. SMC-derived cells are the main cellular component of atherosclerotic lesions and the source of structural components that determine the size of plaques and their propensity to rupture and trigger thrombosis, the proximate cause of heart attack and stroke. Using lineage tracing and single-cell techniques to investigate the full SMC-derived cellular compartment in progressing and regressing plaques in mice, here we show that lowering ApoB-containing lipoproteins reduces nuclear factor kappa-light-chain-enhancer of activated B cells signaling in SMC-derived fibromyocytes and chondromyocytes and leads to depletion of these abundant cell types from plaques. These results uncover an important mechanism through which cholesterol-lowering drugs can achieve plaque regression.
Identifiants
pubmed: 39196190
doi: 10.1038/s44161-023-00412-w
pii: 10.1038/s44161-023-00412-w
doi:
Substances chimiques
Anticholesteremic Agents
0
Cholesterol
97C5T2UQ7J
NF-kappa B
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
203-220Subventions
Organisme : EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))
ID : 866240
Organisme : Novo Nordisk Fonden (Novo Nordisk Foundation)
ID : NNF17OC0030688
Organisme : Aarhus Universitets Forskningsfond (Aarhus University Research Foundation)
ID : AUFF-E-201 9-723
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature Limited.
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