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Effects of β₃-adrenoceptor on scavenger receptor class B type 1 and its signal transduction pathway in apolipoprotein

Yan-qing Guo1, Yan-fang Li, Zhao-hong Wang

  • 1Department of Cardiology, Anzhen Hospital, Capital Medical University, Beijing 100029, China.

European Journal of Pharmacology
|August 6, 2013
PubMed

Insights

Activation of the beta-3 adrenoceptor (β₃-adrenoceptor) reduces atherosclerosis and improves lipid metabolism in apolipoprotein E knockout mice. This suggests a significant anti-atherosclerotic role for β₃-adrenoceptor agonists.

Area of Science:

  • Cardiovascular Research
  • Pharmacology
  • Metabolic Disorders

Background:

  • Beta-3 adrenoceptor (β₃-adrenoceptor) activation is known to improve lipid metabolism disorders.
  • Limited research exists on the anti-atherosclerotic effects of β₃-adrenoceptor in apolipoprotein E knockout (Apoe(-/-)) mice models.
  • Atherosclerosis involves complex lipid metabolism and inflammatory pathways, making it a critical area for therapeutic intervention.

Purpose of the Study:

  • To investigate the effects of β₃-adrenoceptor activation on lipids, atherosclerosis, and related signaling pathways in Apoe(-/-) mice.
  • To evaluate the potential of β₃-adrenoceptor agonists as a therapeutic strategy for atherosclerosis.

Main Methods:

  • Apoe(-/-) mice were fed a high-fat diet and treated with β₃-adrenoceptor agonist, antagonist, saline, or atorvastatin.
  • Serum lipids, thoracic aortic plaque area, lumen area, and protein expression/activity of SR-B1, PKCα, MEK1/2, and ERK1/2 were analyzed.
  • Dose-dependent effects of the β₃-adrenoceptor agonist were assessed by comparing low and high doses.

Main Results:

  • β₃-adrenoceptor agonist treatment significantly reduced serum total cholesterol, triglycerides, and LDL cholesterol, while increasing HDL cholesterol.
  • A significant decrease in atherosclerotic plaque area and an increase in thoracic aortic lumen area were observed in agonist-treated mice.
  • Agonist treatment upregulated hepatic protein kinase Cα (PKCα) activity, scavenger receptor class B type 1 (SR-B1) expression, and downstream signaling molecules (p-MEK1/2, p-ERK1/2).

Conclusions:

  • Activation of β₃-adrenoceptor demonstrates significant anti-atherosclerotic effects in Apoe(-/-) mice by improving lipid profiles and reducing plaque burden.
  • The beneficial effects are mediated, in part, by regulating lipid metabolism and activating the SR-B1 signaling pathway.
  • β₃-adrenoceptor agonists represent a promising therapeutic target for managing atherosclerosis and associated lipid disorders.

Keywords:
LipidsSR-B1Signal transductionβ(3) adrenoceptors

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