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ASSA13-03-17 b3-Adrenoceptor Activation Improves the Formation of Atherosclerosis Plaque in Aged ApoE-Deficient Mice
  1. Wang Zhaohong1,2,
  2. Li Yanfang1,2,
  3. Guo Yanqing1,2
  1. 1Department of Cardiology, Beijing Anzhen Hospital, Capital University of Medical Science
  2. 2Beijing Institute of Heart, Lung and Blood Vessel disease

Abstract

Objective To study the effects of β3-adrenoceptor (β3-AR) activation on atherosclerotic plaque development in aged apolipoprotein E-deficient (ApoE-/-) mice.

Methods Male ApoE-/- mice were fed with a high-fat diet, starting on 10 weeks of age. Starting from 36 weeks of age, mice were randomly treated with atorvastatin (10 mg·kg-1·d-1, by gavage), the β3-AR agonist BRL37344 (1.65 or 3.30 μg·kg-1, twice a week, by intraperitoneal injection), the β3-AR antagonist SR52390A (50 μg·kg-1, twice a week, by intraperitoneal injection), or saline vehicle (twice a week, by intraperitoneal injection) for 12 weeks (n = 10 per group). A group of wild-type C57BL/6J mice receiving normal diet was included as a healthy control. At the end of the 12-week treatment period, serum concentration of lipids were measured. Atherosclerotic plaque in the thoracic aorta was examined using Hematoxy-eosin staining. The extent of fibrosis in the plaque was examined using Masson staining. Western blot was uesed to determine the ApoA-I and SR-BI protein expression. Real-time quantitative PCR was used to determine β3-AR mRNA in the white adipose tissue and the ApoA-I, ApoA-II and SR-BI mRNA expression in liver tissue.

Results High-fat diet in ApoE-/- mice led to hyperlipidemia and the area of and the extent of fibrosis in atherosclerotic plaque (P3-AR mRNA and SR-BI mRNA were lower, ApoA-I and ApoA-II mRNA were higher in ApoE-/- mice (P-/- mice receiving vehicle). Treatment with the β3-AR agonist BRL37344 decreased serum concentration of triglyceride, total cholesterol and non-high density lipoprotein cholesterol. The treatment increased high density lipoprotein cholesterol, downregulated of ApoA-I, ApoA-II and SR-BI expression and upregulated the β3-AR mRNA expression (P-/- mice receiving vehicle). Similar to atorvastatin, BRL37344 treatment dose-dependently reduced the plaque area and collagen content (P-/- mice receiving vehicle at a dose of 3.30 but not 1.65 μg·kg-1). Treatment with the β3-AR antagonist SR52390A did not affect any parameters (P > 0.05 for all measures vs. ApoE-/- mice receiving vehicle).

Conclusions β3-AR agonist impeded the progression of atherosclerosis in ApoE-/- mice, possibly through improvement of lipid profile, ApoA-I, ApoA-II and SR-BI mRNA.

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