Activation of Bone Marrow-Derived Cells Angiotensin (Ang) II Type 1 Receptor by Ang II Promotes Atherosclerotic Plaque Vulnerability.

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License: CC BY 4.0
Serval ID
serval:BIB_DF24A17CD520
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Activation of Bone Marrow-Derived Cells Angiotensin (Ang) II Type 1 Receptor by Ang II Promotes Atherosclerotic Plaque Vulnerability.
Journal
International journal of molecular sciences
Author(s)
Pellegrin M., Bouzourène K., Aubert J.F., Nahimana A., Duchosal M.A., Mazzolai L.
ISSN
1422-0067 (Electronic)
ISSN-L
1422-0067
Publication state
Published
Issued date
04/09/2018
Peer-reviewed
Oui
Volume
19
Number
9
Pages
E2621
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Angiotensin (Ang) II triggers vulnerable atherosclerotic plaque development. Bone marrow (BM)-derived cells are key players in atherogenesis but whether Ang II induces plaque vulnerability directly through Ang II type 1 receptor (AT1R) activation on these cells remains to be clarified. In the present study, we investigated whether a lack of AT1R on BM-derived cells might affect Ang II-mediated vulnerable plaque development. The 2-kidney, 1-clip (2K1C) model (Ang II-dependent mouse model of advanced atherosclerosis and vulnerable plaques) was generated in ApoE <sup>-/-</sup> mice transplanted with AT1aR <sup>-/-</sup> or AT1aR <sup>+/+</sup> BM. Plasma cholesterol as well as hepatic mRNA expression levels of genes involved in cholesterol metabolism were significantly lower in 2K1C mice transplanted with AT1aR <sup>-/-</sup> BM than in controls. Atherosclerotic lesions were significantly smaller in AT1aR <sup>-/-</sup> BM 2K1C mice (-79% in the aortic sinus and -71% in whole aorta compared to controls). Plaques from AT1aR <sup>-/-</sup> BM 2K1C mice exhibited reduced lipid core/fibrous cap and macrophage/smooth muscle cells ratios (-82% and -88%, respectively), and increased collagen content (+70%), indicating a more stable phenotype. Moreover, aortic mRNA levels of pro-inflammatory cytokines IL-12p35, IL-1β, and TNF-α were significantly reduced in AT1aR <sup>-/-</sup> BM 2K1C mice. No significant differences in either the number of circulating Ly6C <sup>high</sup> inflammatory monocytes and Ly6C <sup>low</sup> resident anti-inflammatory monocyte subsets, or in mRNA levels of aortic M1 or M2 macrophage markers were observed between the two groups. No significant differences were observed in splenic mRNA levels of T cell subsets (Th1, Th2, Th17 and Treg) markers between the two groups. In conclusion, direct AT1R activation by Ang II on BM-derived cells promotes hepatic mRNA expression of cholesterol-metabolism-related genes and vascular mRNA expression of pro-inflammatory cytokines that may lead to plaque instability.
Keywords
Angiotensins/adverse effects, Animals, Apolipoproteins E/genetics, Bone Marrow Cells/cytology, Bone Marrow Cells/drug effects, Bone Marrow Transplantation, Cytokines/genetics, Disease Models, Animal, Gene Expression Regulation/drug effects, Gene Knockdown Techniques, Humans, Lipid Metabolism, Liver/drug effects, Liver/metabolism, Mice, Plaque, Atherosclerotic/chemically induced, Plaque, Atherosclerotic/genetics, Plaque, Atherosclerotic/immunology, Receptor, Angiotensin, Type 1/genetics, 2-kidney, 1-clip ApoE−/− mice, Angiotensin II, atherosclerosis, bone marrow transplantation, inflammation, vulnerable plaque
Pubmed
Web of science
Open Access
Yes
Create date
10/09/2018 16:47
Last modification date
30/04/2021 7:15
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