2026-04-27T01:29:55Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/251152025-12-18T13:00:48Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Gunnersen, Stine author Shim, Jeong Tangkjær author Liu, Fan author Tietge, Uwe J F author Sørensen, Charlotte Brandt author Bentzon, Jacob Fog author 2024-03 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. Atheroscler Plus. 2023 Dec 20:55:12-20. 2667-0895 https://hdl.handle.net/20.500.12105/25115 38234375 ATHEROSCLEROSIS PLUS Atherosclerosis CCL2 Inducible knockout Inflammation Smooth muscle cells Conditional deletion of in smooth muscle cells does not reduce early atherosclerosis in mice.