2026-04-27T01:50:05Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/274442026-04-25T00:17:11Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud author Muñiz-Anquela, Rocío author Redondo-Angulo, Ibon author Lewis, Esmeralda A author Lolo, Fidel-Nicolás author González-Cintado, Leticia author Toledano-Donado, Mónica author Pulgarín-Alfaro, Marta author Del Pozo, Miguel A author Bentzon, Jacob Fog 2026-04-24T13:50:49Z 2026-04-24T13:50:49Z 2026-02 Arterioscler Thromb Vasc Biol. 2026 Feb;46(2):e323323. https://hdl.handle.net/20.500.12105/27444 41431924 Arteriosclerosis, Thrombosis, and Vascular Biology Eradicating endothelial caveolae by deleting the (caveolin-1) gene reduces LDL (low-density lipoprotein) uptake in arteries and efficiently prevents early atherogenesis, but the role in established atherosclerosis is unknown. Here, to examine CAV1 as a potential therapeutic target, we deleted endothelial in mice after lesion development and analyzed the effect on LDL uptake and lesion progression. To allow timed endothelium-specific deletion, we generated male and female mice with floxed alleles and endothelium-specific inducible Cre recombinase. Atherosclerosis was induced by virus-mediated PCSK9 (proprotein convertase subtilisin/kexin type 9) gene transfer and a high-cholesterol diet. After 16 weeks of lesion development, endothelial deletion was induced by a series of tamoxifen injections, repeated after 4 weeks, and the mice were followed for another 4 weeks. Mice were injected with fluorescently labeled LDL at 1 and 18 hours before euthanasia to study uptake and retention in lesions. Sections of the aortic root were analyzed for lesion size, composition, and LDL accumulation. Efficient conditional knockout of endothelial was confirmed by CAV1 immunostaining and by the loss of caveolae by electron microscopy. Loss of endothelial for 8 weeks reduced LDL entry into lesions but did not significantly decrease LDL retention, lesion lipid accumulation, fibrous tissue, or lesion size. In males, a reduction in macrophages was seen. Targeting CAV1 does not efficiently block LDL entry or reduce lesion progression in established atherosclerosis. These findings open several questions for further research, including alternative LDL entry mechanisms that could circumvent caveolar transport in established atherosclerosis. eng atherosclerosis caveolin 1 cholesterol endothelium lipoproteins, LDL Progression of Established Atherosclerotic Lesions Is Not Inhibited by Endothelial Knockout of Caveolin-1-Brief Report. research article 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 URL https://repisalud.isciii.es/bitstreams/039f3535-580f-4d0c-80e9-b3c593268a72/download File MD5 204565bcfbb54b2b1e85cc116a459623 3030460 application/pdf Progression of Established Atherosclerotic_Arterioscler Thromb Vasc Biol_2026.pdf