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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Autores principales:	Rolf P Kreutz, Mouhamad Alloosh, Khaled Mansour, et al
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/b8361beb6a714176ae8589855d43c756
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spelling	oai:doaj.org-article:b8361beb6a714176ae8589855d43c7562021-12-02T00:47:43ZMorbid obesity and metabolic syndrome in Ossabaw miniature swine are associated with increased platelet reactivity1178-7007https://doaj.org/article/b8361beb6a714176ae8589855d43c7562011-03-01T00:00:00Zhttp://www.dovepress.com/morbid-obesity-and-metabolic-syndrome-in-ossabaw-miniature-swine-are-a-a6707https://doaj.org/toc/1178-7007Rolf 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 &plusmn; 1.3 &micro;M vs 3.64 &plusmn; 2.2 &micro;M; P = 0.02). MetS pigs demonstrated higher platelet aggregation in response to collagen than lean pigs (area under the curve: 286 &plusmn; 74 vs 198 &plusmn; 123; P = 0.037) and a trend for heightened response to AA (AUC: 260 &plusmn; 151 vs 178 &plusmn; 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 Rolf P KreutzMouhamad AllooshKhaled Mansouret alDove Medical PressarticleSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol 2011, Iss default, Pp 99-105 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Specialties of internal medicine RC581-951
spellingShingle	Specialties of internal medicine RC581-951 Rolf P Kreutz Mouhamad Alloosh Khaled Mansour et al Morbid obesity and metabolic syndrome in Ossabaw miniature swine are associated with increased platelet reactivity
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 &plusmn; 1.3 &micro;M vs 3.64 &plusmn; 2.2 &micro;M; P = 0.02). MetS pigs demonstrated higher platelet aggregation in response to collagen than lean pigs (area under the curve: 286 &plusmn; 74 vs 198 &plusmn; 123; P = 0.037) and a trend for heightened response to AA (AUC: 260 &plusmn; 151 vs 178 &plusmn; 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
format	article
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
title	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_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_sort	morbid obesity and metabolic syndrome in ossabaw miniature swine are associated with increased platelet reactivity
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/b8361beb6a714176ae8589855d43c756
work_keys_str_mv	AT rolfpkreutz morbidobesityandmetabolicsyndromeinossabawminiatureswineareassociatedwithincreasedplateletreactivity AT mouhamadalloosh morbidobesityandmetabolicsyndromeinossabawminiatureswineareassociatedwithincreasedplateletreactivity AT khaledmansour morbidobesityandmetabolicsyndromeinossabawminiatureswineareassociatedwithincreasedplateletreactivity AT etal morbidobesityandmetabolicsyndromeinossabawminiatureswineareassociatedwithincreasedplateletreactivity
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Morbid obesity and metabolic syndrome in Ossabaw miniature swine are associated with increased platelet reactivity

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