Neggazi Samia, Canaple Laurence, Hamlat Nadjiba, Gauthier Karine, Samarut Jacques, Bricca Giampiero, Aouichat-Bouguerra Souhila, Beylot Michel
USTHB, Faculty of Biological Sciences, Laboratory of Biology and Physiology of Organisms (Cellular and Molecular Physiopathology team), BP 32 El Alia, Algiers, Algeria.
Functional Genomics Institute of Lyon, University of Lyon, CNRS, INRA, Ecole Normale Supérieure de Lyon, Lyon, France.
J Vasc Res. 2018;55(4):224-234. doi: 10.1159/000491430. Epub 2018 Aug 9.
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.
甲状腺激素（TH）通过与甲状腺激素受体（TRs）结合来调节基因转录。TRs调节脂质代谢和肾素 - 血管紧张素系统（RAS）的基因。我们研究了ApoE基因敲除小鼠（DKO小鼠）中TRα缺失对以下方面的影响：（i）肝脏和主动脉中控制胆固醇代谢的基因以及组织（t）RAS的表达；（ii）这些基因在培养的血管平滑肌细胞（VSMCs）中的表达以及胆固醇含量的调节。ApoE基因敲除小鼠中TRα的缺失导致肝脏中参与胆固醇合成和流入的基因受到抑制。然而，动脉壁中TRα的缺失抑制了参与胆固醇酯化和排泄的基因的表达，并增强了血管紧张素原（AGT）的表达。ApoE基因敲除小鼠和DKO小鼠的VSMCs在胆固醇加载过程中胆固醇含量增加，但未能增加ATP结合盒转运蛋白A1（ABCA1）的表达。添加T3部分纠正了ApoE基因敲除小鼠细胞中的这些异常，但对DKO小鼠细胞无效。总之，ApoE基因敲除小鼠中TRα的缺失会轻微增加主动脉中tRAS的表达，并加重VSMCs中胆固醇含量的失调。
