Shi Shu-tian, Li Yan-fang, Guo Yan-qing, Wang Zhao-hong
*Department of Cardiology, Anzhen Hospital, Capital Medical University, Beijing, China; and †Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.
J Cardiovasc Pharmacol. 2014 Nov;64(5):407-11. doi: 10.1097/FJC.0000000000000133.
The beta-3 adrenoceptor (β3-AR) protects against the progression of atherosclerosis. However, the specific mechanism of this antiatherosclerotic effect is still not clear. Thus, the aim of this study was to understand the antiatherosclerotic effects of β3-AR. Thirty-six male homozygous apolipoprotein E-deficient mice and wild-type C57BL/6J mice were randomized into 6 treatment groups: wild-type, atherosclerotic model, atorvastatin, low-dose β3-AR agonist, high-dose β3-AR agonist, and β3-AR antagonist groups. The serum lipids, aortic-free cholesterol (FC), and cholesteryl ester (CE) concentrations were measured at the end of the treatments. The mRNA expression levels of liver apolipoprotein A-I (apoA-I), peroxisome proliferator-activated receptor-α (PPARα), and peroxisome proliferator-activated receptor-γ (PPARγ) were detected by quantitative real-time PCR. Protein expression levels of apoA1, PPARα, and PPARγ in the liver were determined by western blot analysis. Treatment with β3-AR significantly increased the plasma levels of high-density lipoprotein cholesterol and apoA-I, whereas the levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol decreased. The β3-AR agonist treatment markedly decreased both the FC and the CE concentrations in the aorta compared with the atherosclerotic model mice. The β3-AR agonist increased the mRNA and protein expression levels of apoA-I, PPARα, and PPARγ in the liver. This study demonstrates that long-term β3-AR activation can regulate lipid metabolic disorders and reduces the aortic FC and the CE concentrations. These effects may be related to apoA-I, PPARα, and PPARγ.
β3肾上腺素能受体（β3-AR）可预防动脉粥样硬化的进展。然而，这种抗动脉粥样硬化作用的具体机制仍不清楚。因此，本研究的目的是了解β3-AR的抗动脉粥样硬化作用。36只雄性纯合载脂蛋白E缺陷小鼠和野生型C57BL/6J小鼠被随机分为6个治疗组：野生型、动脉粥样硬化模型、阿托伐他汀、低剂量β3-AR激动剂、高剂量β3-AR激动剂和β3-AR拮抗剂组。在治疗结束时测量血脂、主动脉游离胆固醇（FC）和胆固醇酯（CE）浓度。通过定量实时PCR检测肝脏载脂蛋白A-I（apoA-I）、过氧化物酶体增殖物激活受体-α（PPARα）和过氧化物酶体增殖物激活受体-γ（PPARγ）的mRNA表达水平。通过蛋白质印迹分析测定肝脏中apoA1、PPARα和PPARγ的蛋白质表达水平。β3-AR治疗显著提高了血浆高密度脂蛋白胆固醇和apoA-I水平，而总胆固醇、甘油三酯和低密度脂蛋白胆固醇水平降低。与动脉粥样硬化模型小鼠相比，β3-AR激动剂治疗显著降低了主动脉中的FC和CE浓度。β3-AR激动剂增加了肝脏中apoA-I、PPARα和PPARγ的mRNA和蛋白质表达水平。本研究表明，长期激活β3-AR可调节脂质代谢紊乱，并降低主动脉FC和CE浓度。这些作用可能与apoA-I、PPARα和PPARγ有关。
