Soft tissue calcification in the Ossabaw miniature pig: experimental and kinetic modeling studies

Abstract

Early stage deposition of calcium into soft tissues is a pre‐cursor to several chronic diseases and an appropriate large animal model is needed. The Ossabaw pig develops metabolic syndrome when fed excess calorie atherogenic diet and progresses to type 2 diabetes and atherosclerosis. Male pigs were fed for 5 months with chow diet (health, lean; n=7) or atherogenic diet (n=8) consisting of chow supplemented with 2% cholesterol, 43% kcal from fat, and 20% kcal from fructose. Pigs were verified to have metabolic syndrome (MetS) by obesity, insulin resistance, impaired glucose tolerance, dyslipidemia, and hypertension. All pigs received intravenous injection of 50nCi/kg of 41Ca and allowed to recover for 1 month, then sacrificed. Blood was drawn at time 0, nearly hourly for the first 24 h, and 1, 2, 3, 6, 8, 10, 15, 20, and 28 days after injection. Peripheral artery segments were harvested from each pig at 4 time points over the 28d recovery. At sacrifice the MetS swine had detectable 41Ca in coronary arteries, but the lean controls had extremely low levels of 41Ca. Intravascular ultrasound showed calcification in MetS, but not lean pigs. A compartmental model of calcium metabolism was developed and deposition into arteries estimated. Through tissue acquisition and kinetics, this pig provides a humanoid model for studying vascular calcification.