Diffuse coronary atherosclerosis in Ossabaw miniature swine with metabolic syndrome compared to Yucatan swine

Abstract

Patients with diabetes have diffuse coronary atherosclerosis, also known as three vessel disease. The Ossabaw miniature swine is an excellent large animal model of metabolic syndrome (pre‐diabetes). Here we compare the pervasiveness of coronary atherosclerosis between the Ossabaw swine model of metabolic syndrome and the widely used Yucatan swine that do not show metabolic syndrome. Each breed was fed two separate diets which were calorie matched and divided into two groups each: control (C) and high fat/cholesterol atherogenic diet (H). Intravascular ultrasound was used to quantify atherosclerosis throughout the epicardial coronary vasculature. Ossabaw swine had increased characteristics of metabolic syndrome including: greater weight gain, glucose intolerance, and insulin resistance, compared to Yucatan. Plasma lipids and blood pressure were not different. H diet increased atherosclerosis ~3‐fold in proximal segments of coronary artery compared to C, with no breed differences. However, Ossabaw H compared to Yucatan H had ~2.5‐fold and ~4‐fold greater atherosclerosis in intermediate and distal coronary segments, respectively. Neointima of Ossabaw had less collagen, suggesting more cellular and/or lipid‐laden composition. We conclude that Ossabaw swine, not Yucatan, exhibit diffuse coronary atherosclerosis, a hallmark of patients with diabetes. Support: NIH RR013223, HL062552.