Thyroid Hormone Receptor Alpha Deletion in ApoE–/– Mice Alters the Arterial Renin-Angiotensin System and Vascular Smooth Muscular Cell Cholesterol Metabolism
| Autor: | Giampiero Bricca, Samia Neggazi, Nadjiba Hamlat, Karine Gauthier, Laurence Canaple, Jacques Samarut, Michel Beylot, S. Aouichat-Bouguerra |
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| Rok vydání: | 2018 |
| Předmět: |
0303 health sciences
medicine.medical_specialty Vascular smooth muscle biology Physiology Cholesterol Lipid metabolism 030204 cardiovascular system & hematology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Endocrinology chemistry Thyroid hormone receptor alpha ABCA1 Internal medicine Renin–angiotensin system biology.protein medicine lipids (amino acids peptides and proteins) Cardiology and Cardiovascular Medicine Receptor 030304 developmental biology Hormone |
| Zdroj: | Journal of Vascular Research. 55:224-234 |
| ISSN: | 1423-0135 1018-1172 |
| DOI: | 10.1159/000491430 |
| Popis: | Thyroid hormone (TH) regulates gene transcription by binding to TH receptors (TRs). TRs regulate the genes of lipid metabolism and the renin-angiotensin system (RAS). We examined the effect of TRα deletion in ApoE–/– mice (DKO mice) on the following: (i) the expression of genes controlling cholesterol metabolism and tissue (t)RAS in the liver and aorta and (ii) the expression of these genes and the regulation of cholesterol content in cultured vascular smooth muscle cells (VSMCs). TRα deletion in ApoE–/– mice led to the repression of genes involved in the synthesis and influx of cholesterol in the liver. However, TRα deletion in the arterial wall suppressed the expression of genes involved in the esterification and excretion of cholesterol and enhanced the expression of angiotensinogen (AGT). The VSMCs of the ApoE–/– and DKO mice increased their cholesterol content during cholesterol loading, but failed to increase the expression of ATP-binding cassette transporter A1 (ABCA1). T3 addition partially corrected these abnormalities in the cells of the ApoE–/– mice but not those of the DKO mice. In conclusion, TRα deletion in ApoE–/– mice slightly increases the expression of tRAS in the aorta and aggravates the dysregulation of cholesterol content in the VSMCs. |
| Databáze: | OpenAIRE |
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