Imai, Takashi, Pasparakis, Manolis ORCID: 0000-0002-9870-0966 and Polykratis, Apostolos (2022). Smooth muscle cell specific NEMO deficiency inhibits atherosclerosis in ApoE(-/-) mice. Sci Rep, 12 (1). BERLIN: NATURE PORTFOLIO. ISSN 2045-2322
Full text not available from this repository.Abstract
The development of atherosclerotic plaques is the result of a chronic inflammatory response coordinated by stromal and immune cellular components of the vascular wall. While endothelial cells and leukocytes are well-recognised mediators of inflammation in atherosclerosis, the role of smooth muscle cells (SMCs) remains incompletely understood. Here we aimed to address the role of canonical NF-kappa B signalling in SMCs in the development of atherosclerosis. We investigated the role of NF-kappa B signalling in SMCs in atherosclerosis by employing SMC-specific ablation of NEMO, an IKK complex subunit that is essential for canonical NF-kappa B activation, in ApoE(-/-) mice. We show that SMC-specific ablation of NEMO (NEMOSMCiKO) inhibited high fat diet induced atherosclerosis in ApoE(-/-) mice. NEMOSMCiKO/ApoE(-/-) mice developed less and smaller atherosclerotic plaques, which contained fewer macrophages, decreased numbers of apoptotic cells and smaller necrotic areas and showed reduced inflammation compared to the plaques of ApoE(-/-) mice. In addition, the plaques of NEMOSMCiKO/ApoE(-/-) mice showed higher expression of alpha-SMA and lower expression of the transcriptional factor KLF4 compared to those of ApoE(-/-) mice. Consistently, in vitro, NEMO-deficient SMCs exhibited reduced proliferation and migration, as well as decreased KLF4 expression and lower production of IL-6 and MCP-1 upon inflammatory stimulus (TNF or LPS) compared to NEMO-expressing SMCs. In conclusion, NEMO-dependent activation of NF-kappa B signalling in SMCs critically contributes to the pathogenesis of atherosclerosis by regulating SMC proliferation, migration and phenotype switching in response to inflammatory stimuli.
Item Type: | Journal Article | ||||||||||||||||
Creators: |
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URN: | urn:nbn:de:hbz:38-661351 | ||||||||||||||||
DOI: | 10.1038/s41598-022-16737-8 | ||||||||||||||||
Journal or Publication Title: | Sci Rep | ||||||||||||||||
Volume: | 12 | ||||||||||||||||
Number: | 1 | ||||||||||||||||
Date: | 2022 | ||||||||||||||||
Publisher: | NATURE PORTFOLIO | ||||||||||||||||
Place of Publication: | BERLIN | ||||||||||||||||
ISSN: | 2045-2322 | ||||||||||||||||
Language: | English | ||||||||||||||||
Faculty: | Unspecified | ||||||||||||||||
Divisions: | Unspecified | ||||||||||||||||
Subjects: | no entry | ||||||||||||||||
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URI: | http://kups.ub.uni-koeln.de/id/eprint/66135 |
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