TRα inhibits arterial renin-angiotensin system expression and prevents cholesterol accumulation in vascular smooth muscle cells
| Autor: | Giampiero Bricca, Karine Gauthier, Souhila Aouichat-Bouguerra, Laurence Canaple, Michel Beylot, Jacques Samarut, Samia Neggazi, Nadjiba Hamlat |
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| Přispěvatelé: | Agressions vasculaires et réponses tissulaires, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Génomique fonctionnelle dans l'athérothrombose (EA 3740), Université de Lyon-Université de Lyon, Physiopathologie Metabolique et Renale, École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
Thyroid Hormones medicine.medical_specialty Vascular smooth muscle Endocrinology Diabetes and Metabolism [SDV]Life Sciences [q-bio] Down-Regulation Cellular homeostasis 030209 endocrinology & metabolism Muscle Smooth Vascular Renin-Angiotensin System Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Endocrinology Internal medicine medicine.artery Renin–angiotensin system Gene expression medicine Animals Cells Cultured ComputingMilieux_MISCELLANEOUS Mice Knockout Regulation of gene expression Aorta Angiotensin II receptor type 1 Cholesterol Arteries General Medicine Atherosclerosis Lipid Metabolism Gene Expression Regulation chemistry 030220 oncology & carcinogenesis cardiovascular system Thyroid Hormone Receptors alpha |
| Zdroj: | Annales d'Endocrinologie Annales d'Endocrinologie, 2019, 80 (2), pp.89-95. ⟨10.1016/j.ando.2018.09.008⟩ Annales d'Endocrinologie, Elsevier Masson, 2019, 80 (2), pp.89-95. ⟨10.1016/j.ando.2018.09.008⟩ |
| ISSN: | 0003-4266 2213-3941 |
| DOI: | 10.1016/j.ando.2018.09.008⟩ |
| Popis: | Objectives The tissue renin-angiotensin system (tRAS) plays a key role in the maintenance of cellular homeostasis but is also implicated in atherosclerosis. Thyroid hormone (TH) contributes, via genomic effects, to control of tRAS gene expression in the arterial wall and vascular smooth muscle cells (VSMCs). We investigated the specific functions of TH receptors-α and -β (TRα and TRβ) on tRAS gene expression in the aorta and VSMCs, and the potential protective effect of TRα against atherosclerosis. Material and methods Using aorta and cultured aortic VSMCs from TRα and TRβ deficient mice, tRAS gene expression was analyzed by determining mRNA levels on real-time PCR. Gene regulation under cholesterol loading mimicking atherosclerosis conditions was also examined in VSMCs in vitro. Results TRα deletion significantly increased expression of angiotensinogen (AGT) and angiotensin II receptor type 1 subtype a (AT1Ra) at transcriptional level in aorta, a tissue with high TRα expression level. TRα activity thus seems to be required for maintenance of physiological levels of AGTand AT1Raexpression in the arterial wall. In addition, during cholesterol loading, TRα deletion significantly increased cholesterol content in VSMCs, with a weaker decrease in AGTexpression. Conclusion TRα seems to have an inhibitory impact on AGTand AT1Raexpression, and loss of TRα function in TRα0/0 mice increases tRAS expression in the aortic wall. More importantly, TRα deletion significantly increases VSMC cholesterol content. Our results are consistent with a protective role of TRα against atherosclerosis. |
| Databáze: | OpenAIRE |
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