Loss of embryonically-derived Kupffer cells during hypercholesterolemia accelerates atherosclerosis development

Rebecca Fima, Sébastien Dussaud, Cheïma Benbida, Margault Blanchet, François Lanthiez, Lucie Poupel, Claudia Brambilla, Adélaïde Gélineau, Mattia Dessena, Marina Blanc, Cédric Lerévérend, Martine Moreau, Alexandre Boissonnas, Emmanuel L. Gautier and Thierry Huby ()
Additional contact information
Rebecca Fima: INSERM, UMRS 1166
Sébastien Dussaud: INSERM, UMRS 1166
Cheïma Benbida: INSERM, UMRS 1166
Margault Blanchet: INSERM, UMRS 1166
François Lanthiez: Sorbonne Université
Lucie Poupel: INSERM, UMRS 1166
Claudia Brambilla: INSERM, UMRS 1166
Adélaïde Gélineau: INSERM, UMRS 1166
Mattia Dessena: INSERM, UMRS 1166
Marina Blanc: INSERM, UMRS 1166
Cédric Lerévérend: INSERM, UMRS 1166
Martine Moreau: INSERM, UMRS 1166
Alexandre Boissonnas: Sorbonne Université
Emmanuel L. Gautier: INSERM, UMRS 1166
Thierry Huby: INSERM, UMRS 1166

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Hypercholesterolemia is a major risk factor for atherosclerosis and associated cardiovascular diseases. The liver plays a key role in the regulation of plasma cholesterol levels and hosts a large population of tissue-resident macrophages known as Kupffer cells (KCs). KCs are located in the hepatic sinusoids where they ensure key functions including blood immune surveillance. However, how KCs homeostasis is affected by the build-up of cholesterol-rich lipoproteins that occurs in the circulation during hypercholesterolemia remains unknown. Here, we show that embryo-derived KCs (EmKCs) accumulate large amounts of lipoprotein-derived cholesterol, in part through the scavenger receptor CD36, and massively expand early after the induction of hypercholesterolemia. After this rapid adaptive response, EmKCs exhibit mitochondrial oxidative stress and their numbers gradually diminish while monocyte-derived KCs (MoKCs) with reduced cholesterol-loading capacities seed the KC pool. Decreased proportion of EmKCs in the KC pool enhances liver cholesterol content and exacerbates hypercholesterolemia, leading to accelerated atherosclerotic plaque development. Together, our data reveal that KC homeostasis is perturbed during hypercholesterolemia, which in turn alters the control of plasma cholesterol levels and increases atherosclerosis.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-52735-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52735-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-52735-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().