Zhao-hong Wang1, Yan-fang Li, Yan-qing Guo. 1. Department of Cardiology, Anzhen Hospital, Capital University of Medical Sciences, Beijing 100029, China.
Abstract
AIM: To examine the effects of β3-adrenoceptor (β3-AR) activation on atherosclerotic plaque development in ApoE(-/-) mice. METHODS: Thirty six week-old male ApoE(-/-) mice on a high-fat diet were treated with atorvastatin (10 mg·kg(-1)·d(-1), po), BRL37344 (β3-AR agonist, 1.65 or 3.30 μg/kg, ip, twice a week) or SR52390A (β3-AR antagonist, 50 μg/kg, ip, twice a week) for 12 weeks. Wild-type C57BL/6J mice receiving a normal diet were taken as healthy controls. At the end of the treatments, serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-high density lipoprotein cholesterol (nHDL-C), glucose and insulin were measured. The thoracic aortas were dissected out, the area of atherosclerotic plaques and extent of fibrosis in the plaques were examined using HE and Masson's trichome staining, respectively. RESULTS: Compared to wild-type mice, ApoE(-/-) mice fed on a high-fat diet exhibited prominent hyperlipidemia and insulin resistance, associated with large area of atherosclerotic plaques and great extent of fibrosis in aortas. Atorvastatin significantly decreased the serum levels of TC and nHDL-C, and reduced the plaque area and collagen content in aortas. BRL37344 significantly decreased the serum levels of TG, TC, nHDL-C, glucose and insulin, and increased HDL-C and the insulin sensitivity, and dose-dependently reduced the plaque area and collagen content in aortas. SR52390A treatment did not affect any parameters studied. CONCLUSION: The β3-AR agonist impedes the progression of atherosclerosis in ApoE(-/-) mice, through improvement of the lipid and glucose profiles.
AIM: To examine the effects of β3-adrenoceptor (β3-AR) activation on atherosclerotic plaque development in ApoE(-/-) mice. METHODS: Thirty six week-old male ApoE(-/-) mice on a high-fat diet were treated with atorvastatin (10 mg·kg(-1)·d(-1), po), BRL37344 (β3-AR agonist, 1.65 or 3.30 μg/kg, ip, twice a week) or SR52390A (β3-AR antagonist, 50 μg/kg, ip, twice a week) for 12 weeks. Wild-type C57BL/6J mice receiving a normal diet were taken as healthy controls. At the end of the treatments, serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-high density lipoprotein cholesterol (nHDL-C), glucose and insulin were measured. The thoracic aortas were dissected out, the area of atherosclerotic plaques and extent of fibrosis in the plaques were examined using HE and Masson's trichome staining, respectively. RESULTS: Compared to wild-type mice, ApoE(-/-) mice fed on a high-fat diet exhibited prominent hyperlipidemia and insulin resistance, associated with large area of atherosclerotic plaques and great extent of fibrosis in aortas. Atorvastatin significantly decreased the serum levels of TC and nHDL-C, and reduced the plaque area and collagen content in aortas. BRL37344 significantly decreased the serum levels of TG, TC, nHDL-C, glucose and insulin, and increased HDL-C and the insulin sensitivity, and dose-dependently reduced the plaque area and collagen content in aortas. SR52390A treatment did not affect any parameters studied. CONCLUSION: The β3-AR agonist impedes the progression of atherosclerosis in ApoE(-/-) mice, through improvement of the lipid and glucose profiles.
Authors: Hyunsook Kim; Patricia A Pennisi; Oksana Gavrilova; Stephanie Pack; William Jou; Jennifer Setser-Portas; Joyce East-Palmer; Yan Tang; Vincent C Manganiello; Derek Leroith Journal: Am J Physiol Endocrinol Metab Date: 2006-06 Impact factor: 4.310
Authors: Susanne Zadelaar; Robert Kleemann; Lars Verschuren; Jitske de Vries-Van der Weij; José van der Hoorn; Hans M Princen; Teake Kooistra Journal: Arterioscler Thromb Vasc Biol Date: 2007-05-31 Impact factor: 8.311