title: β3-Adrenoceptor activation attenuates atherosclerotic plaque formation in ApoE(-/-) mice through lowering blood lipids and glucose.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  The β3-AR agonist impedes the progression of atherosclerosis in ApoE(-/-) mice, through improvement of the lipid and glucose profiles.
authors.affiliation: Department of Cardiology, Anzhen Hospital, Capital University of Medical Sciences, Beijing 100029, China.
authors.forename: Zhao-hong
authors.initials: ZH
authors.lastname: Wang
authors.forename: Yan-fang
authors.initials: YF
authors.lastname: Li
authors.forename: Yan-qing
authors.initials: YQ
authors.lastname: Guo
mesh_terms: D058667:Adrenergic beta-3 Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000037:antagonists & inhibitors / Q000097:blood; D004983:Ethanolamines / Q000494:pharmacology; D008055:Lipids / Q000037:antagonists & inhibitors / Q000097:blood*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000097:blood* / Q000188:drug therapy; D011897:Random Allocation; D022702:Receptors, Adrenergic, beta-3 / Q000096:biosynthesis*
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D001057:Apolipoproteins E; D001786:Blood Glucose; D008076:Cholesterol, HDL; D004983:Ethanolamines; D008055:Lipids; D022702:Receptors, Adrenergic, beta-3; C057368:BRL 37344; D002784:Cholesterol
references.citation: Arterioscler Thromb Vasc Biol. 1999 Apr;19(4):847-53
references.pmid: 10195908
references.citation: Diabetologia. 2009 Jul;52(7):1434-41
references.pmid: 19436992
references.citation: Atherosclerosis. 1987 Dec;68(3):231-40
references.pmid: 3426656
references.citation: FEBS J. 2009 Oct;276(20):5720-8
references.pmid: 19754875
references.citation: J Biol Chem. 1997 Jul 11;272(28):17686-93
references.pmid: 9211919
references.citation: Am J Physiol Endocrinol Metab. 2003 Dec;285(6):E1230-6
references.pmid: 12954594
references.citation: Rom J Morphol Embryol. 2009;50(2):169-79
references.pmid: 19434307
references.citation: Eur J Pharmacol. 2007 Aug 13;569(1-2):155-62
references.pmid: 17574233
references.citation: J Atheroscler Thromb. 2004;11(6):322-9
references.pmid: 15644585
references.citation: Circulation. 2005 Mar 22;111(11):1422-30
references.pmid: 15781753
references.citation: Mol Endocrinol. 1994 Apr;8(4):518-27
references.pmid: 7914350
references.citation: Am J Physiol Endocrinol Metab. 2006 Jun;290(6):E1227-36
references.pmid: 16682489
references.citation: Science. 1992 Oct 16;258(5081):468-71
references.pmid: 1411543
references.citation: Curr Atheroscler Rep. 2004 May;6(3):186-96
references.pmid: 15068743
references.citation: Endocrinology. 1997 Jul;138(7):2697-704
references.pmid: 9202206
references.citation: Diabetes. 2002 Feb;51(2):271-5
references.pmid: 11812732
references.citation: Eur J Pharmacol. 2008 Apr 14;584(1):202-6
references.pmid: 18304529
references.citation: Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5677-81
references.pmid: 8202547
references.citation: Diabetes. 2001 Jan;50(1):113-22
references.pmid: 11147775
references.citation: Nutrition. 2005 Jun;21(6):775-7
references.pmid: 15925305
references.citation: Rev Port Cardiol. 2004 Jan;23(1):95-122
references.pmid: 15058150
references.citation: Endocrinology. 2004 Jan;145(1):269-80
references.pmid: 14551227
references.citation: FEBS Lett. 2007 Oct 30;581(26):5029-33
references.pmid: 17936760
references.citation: Am J Physiol Endocrinol Metab. 2007 Nov;293(5):E1188-97
references.pmid: 17711991
references.citation: Int J Obes. 1983;7(5):409-14
references.pmid: 6139348
references.citation: Arterioscler Thromb Vasc Biol. 2004 Oct;24(10):1755-60
references.pmid: 15319263
references.citation: J Atheroscler Thromb. 2005;12(2):77-84
references.pmid: 15942117
references.citation: Mol Immunol. 2009 Jul;46(11-12):2256-66
references.pmid: 19477016
references.citation: Arterioscler Thromb Vasc Biol. 2003 Feb 1;23(2):183-9
references.pmid: 12588757
references.citation: Eur J Pharmacol. 2005 Jul 25;518(1):71-6
references.pmid: 15979609
references.citation: Clin Chem. 1972 Jun;18(6):499-502
references.pmid: 4337382
references.citation: Arterioscler Thromb Vasc Biol. 2007 Aug;27(8):1706-21
references.pmid: 17541027
references.citation: J Biol Chem. 2001 Jul 20;276(29):27077-82
references.pmid: 11369767
references.citation: Diabetologia. 2006 Aug;49(8):1881-92
references.pmid: 16685502
references.citation: Vascul Pharmacol. 2012 Sep-Oct;57(2-4):91-7
references.pmid: 22609131
references.citation: Methods. 2001 Dec;25(4):402-8
references.pmid: 11846609
references.citation: Atherosclerosis. 1996 Jul;124 Suppl:S11-20
references.pmid: 8831911
references.citation: J Physiol Pharmacol. 2004 Sep;55(3):503-17
references.pmid: 15381823
references.citation: Postgrad Med J. 2005 Jun;81(956):358-66
references.pmid: 15937200
references.citation: J Physiol Pharmacol. 2008 Dec;59 Suppl 7:31-55
references.pmid: 19258656
references.citation: J Biol Chem. 2006 Dec 8;281(49):37794-802
references.pmid: 17032647
references.citation: Biochem Pharmacol. 2001 Jun 15;61(12):1471-8
references.pmid: 11377376
references.citation: Lipids Health Dis. 2011 Oct 12;10:176
references.pmid: 21988829