2026-04-27T01:29:55Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/251152025-12-18T13:00:48Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Gunnersen, Stine
author
Shim, Jeong Tangkjær
author
Liu, Fan
author
Tietge, Uwe J F
author
Sørensen, Charlotte Brandt
author
Bentzon, Jacob Fog
funder
Danish Heart Foundation
funder
Novo Nordisk Foundation
funder
Instituto de Salud Carlos III
funder
Ministerio de Ciencia e Innovación (España)
funder
Ministerio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)
2024-10-15T08:22:21Z
2024-10-15T08:22:21Z
2024-03
Atheroscler Plus. 2023 Dec 20:55:12-20.
2667-0895
https://hdl.handle.net/20.500.12105/25115
38234375
ATHEROSCLEROSIS PLUS
Background and aims: C-C motif chemokine ligand 2 (CCL2) is a pro-inflammatory chemokine important for monocyte recruitment to the arterial wall and atherosclerotic plaques. Global knockout of Ccl2 reduces plaque formation and macrophage content in mice, but the importance of different plaque cell types in mediating this effect has not been resolved. Smooth muscle cells (SMCs) can adopt a potentially pro-inflammatory function with expression of CCL2. The present study aimed to test the hypothesis that SMC-secreted CCL2 is involved in early atherogenesis in mice. Methods: SMC-restricted Cre recombinase was activated at 6 weeks of age in mice with homozygous floxed or wildtype Ccl2 alleles. Separate experiments in mice lacking the Cre recombinase transgene were conducted to control for genetic background effects. Hypercholesterolemia and atherosclerosis were induced by a tail vein injection of recombinant adeno-associated virus (rAAV) encoding proprotein convertase subtilisin/kexin type 9 (PCSK9) and a high-fat diet for 12 weeks. Results: Unexpectedly, mice with SMC-specific Ccl2 deletion developed higher levels of plasma cholesterol and larger atherosclerotic plaques with more macrophages compared with wild-type littermates. When total cholesterol levels were incorporated into the statistical analysis, none of the effects on plaque development between groups remained significant. Importantly, changes in plasma cholesterol and atherosclerosis remained in mice lacking Cre recombinase indicating that they were not caused by SMC-specific CCL2 deletion but by effects of the floxed allele or passenger genes. Conclusions: SMC-specific deficiency of Ccl2 does not significantly affect early plaque development in hypercholesterolemic mice.
eng
Atherosclerosis
CCL2
Inducible knockout
Inflammation
Smooth muscle cells
Conditional deletion of in smooth muscle cells does not reduce early atherosclerosis in mice.
research article
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URL
https://repisalud.isciii.es/bitstreams/a265e6de-6e39-4bd0-8b5d-ced7f7855672/download
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Atheroscler Plus_2023_Conditional deletion of Ccl2.pdf
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https://repisalud.isciii.es/bitstreams/b9fb3980-4a84-4ce5-b499-70a7351a87a1/download
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text/plain
Atheroscler Plus_2023_Conditional deletion of Ccl2.pdf.txt