Morbid obesity and metabolic syndrome in Ossabaw miniature swine are associated with increased platelet reactivity
Rolf P Kreutz1,2, Mouhamad Alloosh3, Khaled Mansour1, Zachary Neeb3, Yvonne Kreutz2, David A Flockhart2, Michael Sturek31Krannert Institute of Cardiology, 2Division of Clinical Pharmacology, 3Department of Cellular and Integrative Physiology, Indiana University School of Medicine, IN, USABackground:...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2011-03-01
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| Series: | Diabetes, Metabolic Syndrome and Obesity |
| Online Access: | http://www.dovepress.com/morbid-obesity-and-metabolic-syndrome-in-ossabaw-miniature-swine-are-a-a6707 |
| _version_ | 1811174238371971072 |
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| author | Rolf P Kreutz Mouhamad Alloosh Khaled Mansour et al |
| author_facet | Rolf P Kreutz Mouhamad Alloosh Khaled Mansour et al |
| author_sort | Rolf P Kreutz |
| collection | DOAJ |
| description | Rolf P Kreutz1,2, Mouhamad Alloosh3, Khaled Mansour1, Zachary Neeb3, Yvonne Kreutz2, David A Flockhart2, Michael Sturek31Krannert Institute of Cardiology, 2Division of Clinical Pharmacology, 3Department of Cellular and Integrative Physiology, Indiana University School of Medicine, IN, USABackground: Metabolic syndrome (MetS) and type 2 diabetes mellitus in humans are associated with increased platelet activation and hyperreactivity of platelets to various agonists. Ossabaw swine develop all the hallmarks of MetS including obesity, insulin resistance, hypertension, dyslipidemia, endothelial dysfunction, and coronary artery disease when being fed excess calorie atherogenic diet. We hypothesized that Ossabaw swine with MetS would exhibit increased platelet reactivity compared with lean pigs without MetS.Materials and methods: Ossabaw swine were fed high caloric, atherogenic diet for 44 weeks to induce MetS (n = 10) and were compared with lean controls without MetS that had been fed normal calorie standard diet (n = 10). Light transmittance aggregometry was performed using adenosine diphosphate (ADP), collagen, thrombin, and arachidonic acid (AA) at different concentrations. Dose response curves and EC50 were calculated. Glucose tolerance testing and intravascular ultrasound study of coronary arteries were performed.Results: MetS pigs compared with lean controls were morbidly obese, showed evidence of arterial hypertension, elevated cholesterol, low-density lipoprotein/high-density lipoprotein, and triglycerides, and insulin resistance. Platelets from MetS pigs were more sensitive to ADP-induced platelet aggregation than leans (EC50: 1.83 ± 1.3 µM vs 3.64 ± 2.2 µM; P = 0.02). MetS pigs demonstrated higher platelet aggregation in response to collagen than lean pigs (area under the curve: 286 ± 74 vs 198 ± 123; P = 0.037) and a trend for heightened response to AA (AUC: 260 ± 151 vs 178 ± 145; P = 0.13). No significant difference was found for platelet aggregation in response to thrombin.Conclusions: MetS in Ossabaw swine is associated with increased reactivity of platelets to ADP and collagen. The Ossabaw swine may be a practical, large animal model for the study of certain aspects of platelet pathophysiology and examine vascular devices in a metabolic environment comparable to humans with MetS.Keywords: coronary artery disease, insulin resistance, glucose intolerance, platelet |
| first_indexed | 2024-04-10T17:59:45Z |
| format | Article |
| id | doaj.art-b8361beb6a714176ae8589855d43c756 |
| institution | Directory Open Access Journal |
| issn | 1178-7007 |
| language | English |
| last_indexed | 2024-04-10T17:59:45Z |
| publishDate | 2011-03-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Diabetes, Metabolic Syndrome and Obesity |
| spelling | doaj.art-b8361beb6a714176ae8589855d43c7562023-02-02T16:16:09ZengDove Medical PressDiabetes, Metabolic Syndrome and Obesity1178-70072011-03-012011default99105Morbid obesity and metabolic syndrome in Ossabaw miniature swine are associated with increased platelet reactivityRolf P KreutzMouhamad AllooshKhaled Mansouret alRolf P Kreutz1,2, Mouhamad Alloosh3, Khaled Mansour1, Zachary Neeb3, Yvonne Kreutz2, David A Flockhart2, Michael Sturek31Krannert Institute of Cardiology, 2Division of Clinical Pharmacology, 3Department of Cellular and Integrative Physiology, Indiana University School of Medicine, IN, USABackground: Metabolic syndrome (MetS) and type 2 diabetes mellitus in humans are associated with increased platelet activation and hyperreactivity of platelets to various agonists. Ossabaw swine develop all the hallmarks of MetS including obesity, insulin resistance, hypertension, dyslipidemia, endothelial dysfunction, and coronary artery disease when being fed excess calorie atherogenic diet. We hypothesized that Ossabaw swine with MetS would exhibit increased platelet reactivity compared with lean pigs without MetS.Materials and methods: Ossabaw swine were fed high caloric, atherogenic diet for 44 weeks to induce MetS (n = 10) and were compared with lean controls without MetS that had been fed normal calorie standard diet (n = 10). Light transmittance aggregometry was performed using adenosine diphosphate (ADP), collagen, thrombin, and arachidonic acid (AA) at different concentrations. Dose response curves and EC50 were calculated. Glucose tolerance testing and intravascular ultrasound study of coronary arteries were performed.Results: MetS pigs compared with lean controls were morbidly obese, showed evidence of arterial hypertension, elevated cholesterol, low-density lipoprotein/high-density lipoprotein, and triglycerides, and insulin resistance. Platelets from MetS pigs were more sensitive to ADP-induced platelet aggregation than leans (EC50: 1.83 ± 1.3 µM vs 3.64 ± 2.2 µM; P = 0.02). MetS pigs demonstrated higher platelet aggregation in response to collagen than lean pigs (area under the curve: 286 ± 74 vs 198 ± 123; P = 0.037) and a trend for heightened response to AA (AUC: 260 ± 151 vs 178 ± 145; P = 0.13). No significant difference was found for platelet aggregation in response to thrombin.Conclusions: MetS in Ossabaw swine is associated with increased reactivity of platelets to ADP and collagen. The Ossabaw swine may be a practical, large animal model for the study of certain aspects of platelet pathophysiology and examine vascular devices in a metabolic environment comparable to humans with MetS.Keywords: coronary artery disease, insulin resistance, glucose intolerance, platelethttp://www.dovepress.com/morbid-obesity-and-metabolic-syndrome-in-ossabaw-miniature-swine-are-a-a6707 |
| spellingShingle | Rolf P Kreutz Mouhamad Alloosh Khaled Mansour et al Morbid obesity and metabolic syndrome in Ossabaw miniature swine are associated with increased platelet reactivity Diabetes, Metabolic Syndrome and Obesity |
| title | Morbid obesity and metabolic syndrome in Ossabaw miniature swine are associated with increased platelet reactivity |
| title_full | Morbid obesity and metabolic syndrome in Ossabaw miniature swine are associated with increased platelet reactivity |
| title_fullStr | Morbid obesity and metabolic syndrome in Ossabaw miniature swine are associated with increased platelet reactivity |
| title_full_unstemmed | Morbid obesity and metabolic syndrome in Ossabaw miniature swine are associated with increased platelet reactivity |
| title_short | Morbid obesity and metabolic syndrome in Ossabaw miniature swine are associated with increased platelet reactivity |
| title_sort | morbid obesity and metabolic syndrome in ossabaw miniature swine are associated with increased platelet reactivity |
| url | http://www.dovepress.com/morbid-obesity-and-metabolic-syndrome-in-ossabaw-miniature-swine-are-a-a6707 |
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