title: Metabolic syndrome and coronary artery disease in Ossabaw compared with Yucatan swine.
abstract: Metabolic syndrome (MetS), a compilation of associated risk factors, increases the risk of type 2 diabetes and coronary artery disease (CAD, atherosclerosis), which can progress to the point of artery occlusion. Stents are the primary interventional treatment for occlusive CAD, and patients with MetS and hyperinsulinemia have increased restenosis. Because of its thrifty genotype, the Ossabaw pig is a model of MetS. We tested the hypothesis that, when fed high-fat diet, Ossabaw swine develop more features of MetS, greater native CAD, and greater stent-induced CAD than do Yucatan swine. Animals of each breed were divided randomly into 2 groups and fed 2 different calorie-matched diets for 40 wk: control diet (C) and high-fat, high-cholesterol atherogenic diet (H). A bare metal stent was placed in the circumflex artery, and pigs were allowed to recover for 3 wk. Characteristics of MetS, macrovascular and microvascular CAD, in-stent stenosis, and Ca(2+) signaling in coronary smooth muscle cells were evaluated. MetS characteristics including, obesity, glucose intolerance, hyperinsulinemia, and elevated arterial pressure were elevated in Ossabaw swine compared to Yucatan swine. Ossabaw swine with MetS had more extensive and diffuse native CAD and in-stent stenosis and impaired coronary blood flow regulation compared with Yucatan. In-stent atherosclerotic lesions in Ossabaw coronary arteries were less fibrous and more cellular. Coronary smooth muscle cells from Ossabaw had impaired Ca(2+) efflux and intracellular sequestration versus cells from Yucatan swine. Therefore, Ossabaw swine are a superior model of MetS, subsequent CAD, and cellular Ca(2+) signaling defects, whereas Yucatan swine are leaner and relatively resistant to MetS and CAD.
authors.affiliation: Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Zachary P
authors.initials: ZP
authors.lastname: Neeb
authors.forename: Jason M
authors.initials: JM
authors.lastname: Edwards
authors.forename: Mouhamad
authors.initials: M
authors.lastname: Alloosh
authors.forename: Xin
authors.initials: X
authors.lastname: Long
authors.forename: Eric A
authors.initials: EA
authors.lastname: Mokelke
authors.forename: Michael
authors.initials: M
authors.lastname: Sturek
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure; D015992:Body Mass Index; D001835:Body Weight; D002118:Calcium / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000009:adverse effects*; D003324:Coronary Artery Disease / Q000209:etiology* / Q000473:pathology*; D003326:Coronary Circulation / Q000187:drug effects; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D024821:Metabolic Syndrome / Q000150:complications / Q000209:etiology* / Q000473:pathology*; D013045:Species Specificity; D015607:Stents; D013552:Swine
chemical_list: D002791:Cholesterol, Dietary; D002118:Calcium
references.citation: Am J Physiol Heart Circ Physiol. 2009 Nov;297(5):H1629-37
references.pmid: 19749164
references.citation: Coron Artery Dis. 2008 Jun;19(4):217-26
references.pmid: 18480664
references.citation: Diabetologia. 2000 May;43(5):632-41
references.pmid: 10855538
references.citation: Toxicol Pathol. 2006;34(1):11-8
references.pmid: 16507539
references.citation: Am J Physiol Heart Circ Physiol. 2008 Jun;294(6):H2489-96
references.pmid: 18390821
references.citation: Arterioscler Thromb Vasc Biol. 2009 May;29(5):781-6
references.pmid: 19229071
references.citation: Circulation. 2005 Nov 15;112(20):3066-72
references.pmid: 16275870
references.citation: Comp Med. 2006 Feb;56(1):35-45
references.pmid: 16521858
references.citation: Diabetes Care. 2005 Apr;28(4):873-7
references.pmid: 15793188
references.citation: Am J Physiol Heart Circ Physiol. 2010 Apr;298(4):H1182-9
references.pmid: 20118408
references.citation: Science. 2001 Dec 7;294(5549):2166-70
references.pmid: 11739957
references.citation: J Am Coll Cardiol. 2000 Sep;36(3):731-8
references.pmid: 10987592
references.citation: Obes Surg. 2007 Oct;17(10):1332-9
references.pmid: 18098400
references.citation: Diabetes. 1982;31(Suppl 1 Pt 2):30-6
references.pmid: 6761193
references.citation: ILAR J. 2004;45(3):303-13
references.pmid: 15229377
references.citation: Ann N Y Acad Sci. 2002 Jun;967:414-23
references.pmid: 12079869
references.citation: Nutr Rev. 2002 Oct;60(10 Pt 2):S1-14; discussion S68-84, 85-7
references.pmid: 12403078
references.citation: Dis Markers. 2009;26(2):75-83
references.pmid: 19407362
references.citation: Atherosclerosis. 2003 Mar;167(1):15-23
references.pmid: 12618264
references.citation: J Physiol. 1995 Jan 15;482 ( Pt 2):259-74
references.pmid: 7536247
references.citation: Cardiovasc Res. 2010 Feb 1;85(3):631-40
references.pmid: 19744946
references.citation: Circulation. 2002 Oct 1;106(14):1867-73
references.pmid: 12356643
references.citation: ILAR J. 2006;47(3):243-58
references.pmid: 16804199
references.citation: J Clin Endocrinol Metab. 2007 Feb;92(2):399-404
references.pmid: 17284640
references.citation: Physiol Rev. 2004 Jul;84(3):767-801
references.pmid: 15269336
references.citation: Proc Soc Exp Biol Med. 1973 May;143(1):198-203
references.pmid: 4703428
references.citation: Arterioscler Thromb Vasc Biol. 2009 Sep;29(9):1342-8
references.pmid: 19520975
references.citation: J Appl Physiol (1985). 2004 Mar;96(3):1069-79
references.pmid: 14634027
references.citation: J Pharmacol Exp Ther. 2003 Jul;306(1):132-40
references.pmid: 12663685
references.citation: Circ Res. 2004 Aug 20;95(4):406-14
references.pmid: 15256479
references.citation: Atherosclerosis. 2001 Nov;159(1):117-24
references.pmid: 11689213
references.citation: Circ Res. 2007 May 25;100(10):1415-27
references.pmid: 17525381
references.citation: J Lipid Res. 2002 Oct;43(10):1618-29
references.pmid: 12364546
references.citation: Diabetes. 1955 Sep-Oct;4(5):367-76
references.pmid: 13270659
references.citation: Am J Physiol Heart Circ Physiol. 2010 Mar;298(3):H966-73
references.pmid: 20044440
references.citation: Am J Physiol Endocrinol Metab. 2005 Feb;288(2):E412-21
references.pmid: 15479954
references.citation: Comp Med. 2003 Feb;53(1):53-64
references.pmid: 12625507
references.citation: N Engl J Med. 2007 Feb 22;356(8):830-40
references.pmid: 17314342
references.citation: J Vasc Res. 2001 Sep-Oct;38(5):432-43
references.pmid: 11561145
references.citation: Clin Chem. 1972 Jun;18(6):499-502
references.pmid: 4337382
references.citation: Diabetes Obes Metab. 2007 Nov;9 Suppl 2:170-9
references.pmid: 17919191
references.citation: Lancet. 2007 Feb 24;369(9562):667-78
references.pmid: 17321312
references.citation: J Am Coll Cardiol. 2008 Jul 22;52(4):255-62
references.pmid: 18634979
references.citation: Circ Res. 2006 Mar 3;98(4):557-63
references.pmid: 16439693
references.citation: Comp Med. 2005 Oct;55(5):445-51
references.pmid: 16270901
references.citation: Am J Med. 1994 Mar;96(3):260-73
references.pmid: 8154515
references.citation: Lab Anim. 1999 Apr;33(2):129-34
references.pmid: 10780815
references.citation: J Nutr. 1982 Dec;112(12):2307-13
references.pmid: 6754889
references.citation: J Appl Physiol (1985). 2003 Sep;95(3):1301-4
references.pmid: 12754176
references.citation: Catheter Cardiovasc Interv. 2003 Dec;60(4):515-23
references.pmid: 14624433
references.citation: Hypertension. 2003 Mar;41(3 Pt 2):625-33
references.pmid: 12623970
references.citation: Am J Physiol Endocrinol Metab. 2002 Jun;282(6):E1342-51
references.pmid: 12006365
references.citation: J Pharmacol Exp Ther. 2000 Nov;295(2):484-91
references.pmid: 11046079
references.citation: J Appl Physiol (1985). 2006 Sep;101(3):752-62
references.pmid: 16763107
references.citation: Circulation. 2004 Jan 27;109(3):433-8
references.pmid: 14744958
references.citation: Circulation. 2006 Jun 27;113(25):2943-6
references.pmid: 16801475
references.citation: Am J Cardiol. 2008 Jun 1;101(11):1679
references.pmid: 18489952
references.citation: Comp Med. 2007 Oct;57(5):493-504
references.pmid: 17974133
references.citation: Clin Chem. 2002 Mar;48(3):436-72
references.pmid: 11861436
references.citation: J Appl Physiol (1985). 2003 Sep;95(3):1179-93
references.pmid: 12777409
references.citation: Circulation. 2003 Oct 28;108(17):2074-81
references.pmid: 14530196
references.citation: J Appl Physiol (1985). 2005 Feb;98(2):461-7
references.pmid: 15465890
references.citation: Hepatology. 2009 Jul;50(1):56-67
references.pmid: 19434740
references.citation: Clin Chem. 1982 Jun;28(6):1379-88
references.pmid: 7074948
references.citation: Am J Physiol. 1990 Aug;259(2 Pt 2):H643-7
references.pmid: 2386234
references.citation: Diabetes. 2003 Jan;52(1):118-23
references.pmid: 12502501
references.citation: Am J Physiol Heart Circ Physiol. 2002 Dec;283(6):H2397-410
references.pmid: 12388302
references.citation: Diabetes. 1996 Jul;45(7):876-80
references.pmid: 8666136
references.citation: Thromb Haemost. 1999 May;81(5):835-43
references.pmid: 10365761
references.citation: Coron Artery Dis. 2008 Feb;19(1):27-31
references.pmid: 18281812
references.citation: J Am Coll Cardiol. 1999 Oct;34(4):1045-9
references.pmid: 10520788
references.citation: Med Sci Sports Exerc. 2005 Jul;37(7):1119-25
references.pmid: 16015127
references.citation: Metabolism. 2004 Aug;53(8):1021-6
references.pmid: 15281012
references.citation: J Nutr. 1982 Jan;112(1):104-11
references.pmid: 7033485
references.citation: Comp Med. 2002 Dec;52(6):523-9
references.pmid: 12540165
references.citation: Diabetes Care. 2004 Jun;27(6):1487-95
references.pmid: 15161807
references.citation: Am J Physiol Endocrinol Metab. 2006 Apr;290(4):E670-7
references.pmid: 16278249
references.citation: Comp Med. 2003 Feb;53(1):42-52
references.pmid: 12625506
references.citation: Am J Physiol Heart Circ Physiol. 2005 Mar;288(3):H1233-41
references.pmid: 15528227
references.citation: Exp Biol Med (Maywood). 2009 Jun;234(6):683-92
references.pmid: 19307464
references.citation: Comp Med. 2008 Apr;58(2):168-73
references.pmid: 18524175
references.citation: Diabetes. 2001 Jul;50(7):1654-65
references.pmid: 11423488
references.citation: Heart. 2004 Jul;90(7):732-8
references.pmid: 15201238
references.citation: J Appl Physiol (1985). 1991 Nov;71(5):1764-73
references.pmid: 1761472
references.citation: J Am Vet Med Assoc. 2001 Mar 1;218(5):669-96
references.pmid: 11280396
references.citation: J Biomed Opt. 2007 Sep-Oct;12(5):054007
references.pmid: 17994895
references.citation: J Vasc Res. 2002 May-Jun;39(3):208-20
references.pmid: 12097819
references.citation: Am J Physiol Heart Circ Physiol. 2001 Jul;281(1):H223-31
references.pmid: 11406489
references.citation: Metabolism. 1998 Dec;47(12):1520-4
references.pmid: 9867084