Activation of Bone Marrow-Derived Cells Angiotensin (Ang) II Type 1 Receptor by Ang II Promotes Atherosclerotic Plaque Vulnerability
| العنوان: | Activation of Bone Marrow-Derived Cells Angiotensin (Ang) II Type 1 Receptor by Ang II Promotes Atherosclerotic Plaque Vulnerability |
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| المؤلفون: | Jean-François Aubert, Aimable Nahimana, Maxime Pellegrin, Lucia Mazzolai, Michel A. Duchosal, Karima Bouzourene |
| المصدر: | International journal of molecular sciences, vol. 19, no. 9, pp. E2621 International Journal of Molecular Sciences Volume 19 Issue 9 International Journal of Molecular Sciences, Vol 19, Iss 9, p 2621 (2018) |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, 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, 030204 cardiovascular system & hematology, medicine.disease_cause, lcsh:Chemistry, 0302 clinical medicine, Receptor, lcsh:QH301-705.5, Spectroscopy, Chemistry, General Medicine, M2 Macrophage, Plaque, Atherosclerotic, Computer Science Applications, medicine.anatomical_structure, Liver, cardiovascular system, Cytokines, medicine.symptom, hormones, hormone substitutes, and hormone antagonists, medicine.medical_specialty, Angiotensins, T cell, Inflammation, Bone Marrow Cells, Catalysis, Article, Receptor, Angiotensin, Type 1, Inorganic Chemistry, 03 medical and health sciences, Apolipoproteins E, Internal medicine, Renin–angiotensin system, medicine, Physical and Theoretical Chemistry, Molecular Biology, Organic Chemistry, Vulnerable plaque, 030104 developmental biology, Endocrinology, lcsh:Biology (General), lcsh:QD1-999, Gene Expression Regulation, Bone marrow |
| الوصف: | 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&minus /&minus mice transplanted with AT1aR&minus or AT1aR+/+ 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&minus BM than in controls. Atherosclerotic lesions were significantly smaller in AT1aR&minus BM 2K1C mice (&minus 79% in the aortic sinus and &minus 71% in whole aorta compared to controls). Plaques from AT1aR&minus BM 2K1C mice exhibited reduced lipid core/fibrous cap and macrophage/smooth muscle cells ratios (&minus 82% and &minus 88%, respectively), and increased collagen content (+70%), indicating a more stable phenotype. Moreover, aortic mRNA levels of pro-inflammatory cytokines IL-12p35, IL-1&beta and TNF-&alpha were significantly reduced in AT1aR&minus BM 2K1C mice. No significant differences in either the number of circulating Ly6Chigh inflammatory monocytes and Ly6Clow 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6cee0e037492a17ef790c3af169b1a34 https://serval.unil.ch/resource/serval:BIB_DF24A17CD520.P001/REF.pdf |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....6cee0e037492a17ef790c3af169b1a34 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |