Swine Disease Models for Optimal Vascular Engineering

Abstract

Swine disease models are essential for mimicry of human metabolic and vascular pathophysiology, thereby enabling high-fidelity translation to human medicine. The worldwide epidemic of obesity, metabolic disease, and diabetes has prompted the focus on these diseases in this review. We highlight the remarkable similarity between Ossabaw miniature swine and humans with metabolic syndrome and atherosclerosis. Although the evidence is strongest for swine models of coronary artery disease, findings are generally applicable to any vascular bed. We discuss the major strengths and weaknesses of swine models. The development of vascular imaging is an example of optimal vascular engineering in swine. Although challenges regarding infrastructure and training of engineers in the use of swine models exist, opportunities are ripe for gene editing, studies of molecular mechanisms, and use of swine in coronary artery imaging and testing of devices that can move quickly to human clinical studies.

Atherosclerosis Imaging with 18F-Sodium Fluoride PET

“…Furthermore, as Hsu et al [ 28 ] noted, it is possible that coronary artery calcification could be modulated very differently by exercise than aortic calcification. Large animal models will be essential for elucidating coronary artery calcification mechanisms in disease [ 30 ].…”

Animal Models for COVID-19: More to the Picture Than ACE2, Rodents, Ferrets, and Non-human Primates. A Case for Porcine Respiratory Coronavirus and the Obese Ossabaw Pig

“…This is especially true for the Ossabaw pig that has been described as having the greatest capacity of any known, terrestrial mammal to produce and store fat (Brisbin and Mayer, 2001). We, and others, have documented that high energy and high fat diets result in the rapid occurrence of obesity in Ossabaw pigs (Sturek et al, 2020). This reproducibly leads to a metabolic syndrome state with clinical signs such as hypertension, high fasting blood glucose, and dyslipidemia, with more advanced end-points such as pre-diabetes, non-alcoholic steatohepatitis (NASH), and cardiovascular disease routinely achieved.…”

“…We would like to emphasize that in addition to closely mirroring human physiology, anatomy, immunology and food preferences, a number of pig breeds have been extensively documented to be an excellent model for human diet-induced obesity including the spectrum of inflammation-related co-morbidities associated with this condition (metabolic syndrome; Sturek et al, 2020). This is especially true for the Ossabaw pig that has been described as having the greatest capacity of any known, terrestrial mammal to produce and store fat (Brisbin and Mayer, 2001).…”

The genome of the naturally evolved obesity-prone Ossabaw miniature pig

“…Generally for complex and systemic diseases, pigs are superior to rodent models, as they are much more similar to humans with respect to e.g., the cardiovascular system, inflammation phenotypes and mechanisms, and organ sizes ( Zettler et al., 2020 ). Moreover, certain types of pigs have a phenomenal propensity to obesity and this is especially the case for the Ossabaw pig, which is an outstanding human translatable obesity model ( Sturek et al., 2020 ). Obesity in the Ossabaw pig is reproducibly and rapidly obtained by high energy high fat dieting, presenting as robust MetS ( Neeb et al., 2010 ; Sturek et al., 2020 ), closely resembling the state observed in metabolically unhealthy obese humans ( O'Neill and O'Driscoll, 2015 ).…”

“…Moreover, certain types of pigs have a phenomenal propensity to obesity and this is especially the case for the Ossabaw pig, which is an outstanding human translatable obesity model ( Sturek et al., 2020 ). Obesity in the Ossabaw pig is reproducibly and rapidly obtained by high energy high fat dieting, presenting as robust MetS ( Neeb et al., 2010 ; Sturek et al., 2020 ), closely resembling the state observed in metabolically unhealthy obese humans ( O'Neill and O'Driscoll, 2015 ). Notably, the Ossabaw pig is a feral pig breed developed in isolation for approximately 500 years by natural evolution ( Sturek et al., 2015 ) on Ossabaw Island (Georgia, USA), host to the only wild-living colony in the world.…”