Back to Browse Journals » Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy » Volume 4

Morbid obesity and metabolic syndrome in Ossabaw miniature swine are associated with increased platelet reactivity

Authors Rolf P Kreutz, Mouhamad Alloosh, Khaled Mansour, et al

Published 15 March 2011 Volume 2011:4 Pages 99—105


Review by Single-blind

Peer reviewer comments 3

Rolf P Kreutz1,2, Mouhamad Alloosh3, Khaled Mansour1, Zachary Neeb3, Yvonne Kreutz2, David A Flockhart2, Michael Sturek3
1Krannert Institute of Cardiology, 2Division of Clinical Pharmacology, 3Department of Cellular and Integrative Physiology, Indiana University School of Medicine, IN, USA

Background: 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

Download Article [PDF] View Full Text [HTML] 

Creative Commons License This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution - Non Commercial (unported, v3.0) License. The full terms of the License are available at Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at:

Other articles by this author:

Cytochrome P450 3A4*22, PPAR-α, and ARNT polymorphisms and clopidogrel response

Kreutz RP, Owens J, Jin Y, Nystrom P, Desta Z, Kreutz Y, Breall JA, Li L, Chiang CW, Kovacs RJ, Flockhart DA

Clinical Pharmacology: Advances and Applications 2013, 5:185-192

Published Date: 9 December 2013

Influence of paraoxonase-1 Q192R and cytochrome P450 2C19 polymorphisms on clopidogrel response

Kreutz RP, Nystrom P, Kreutz Y, Miao J, Desta Z, Breall JA, Li L, Chiang C, Kovacs R, Flockhart DA, Jin Y

Clinical Pharmacology: Advances and Applications 2012, 4:13-20

Published Date: 20 February 2012

Readers of this article also read:

Chloronychia: green nail syndrome caused by Pseudomonas aeruginosa in elderly persons

Chiriac A, Brzezinski P, Foia L, Marincu I

Clinical Interventions in Aging 2015, 10:265-267

Published Date: 14 January 2015

A new recombinant factor VIII: from genetics to clinical use

Santagostino E

Drug Design, Development and Therapy 2014, 8:2507-2515

Published Date: 12 December 2014

Patient preference and ease of use for different coagulation factor VIII reconstitution device scenarios: a cross-sectional survey in five European countries

Cimino E, Linari S, Malerba M, Halimeh S, Biondo F, Westfeld M

Patient Preference and Adherence 2014, 8:1713-1720

Published Date: 12 December 2014

A qualitative study on hypertensive care behavior in primary health care settings in Malaysia

Shima R, Farizah MH, Majid HA

Patient Preference and Adherence 2014, 8:1597-1609

Published Date: 17 November 2014

Managing hemophilia: the role of mobile technology

Khair K, Holland M

Smart Homecare Technology and TeleHealth 2014, 2:39-44

Published Date: 6 May 2014

Treatment of patients with von Willebrand disease

Tuohy E, Litt E, Alikhan R

Journal of Blood Medicine 2011, 2:49-57

Published Date: 20 April 2011

The use of PEGylated liposomes in the development of drug delivery applications for the treatment of hemophilia

Rivka Yatuv, Micah Robinson, Inbal Dayan-Tarshish, et al

International Journal of Nanomedicine 2010, 5:581-591

Published Date: 6 August 2010

Critical appraisal of the role of recombinant activated factor VII in the treatment of hemophilia patients with inhibitors

Ampaiwan Chuansumrit, Pantep Angchaisuksiri, Nongnuch Sirachainan

Journal of Blood Medicine 2010, 1:37-48

Published Date: 30 March 2010