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

Rolf P. Kreutz, Mouhamad Alloosh, Khaled Mansour, Zachary Neeb, Yvonne Kreutz, David A. Flockhart, Michael Sturek

25 Scopus citations

Abstract

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 ADPinduced 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.

Original languageEnglish (US)
Pages (from-to)99-105
Number of pages7
JournalDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy
Volume4
DOIs
StatePublished - Jan 1 2011

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Keywords

  • Coronary artery disease
  • Glucose intolerance
  • Insulin resistance
  • Platelet

ASJC Scopus subject areas

  • Pharmacology
  • Internal Medicine

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