Metabolic syndrome and coronary artery disease in Ossabaw compared with Yucatan swine.
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.
Neeb
Zachary P
ZP
Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana.
Edwards
Jason M
JM
Alloosh
Mouhamad
M
Long
Xin
X
Mokelke
Eric A
EA
Sturek
Michael
M
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
D002791:Cholesterol, Dietary; D002118:Calcium
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