Animal models of atherosclerosis have proven to be an invaluable asset in understanding the pathogenesis of the disease. However, large animal models may be needed in order to assess novel therapeutic approaches to the treatment of atherosclerosis. Porcine models of coronary and peripheral atherosclerosis offer several advantages over rodent models, including similar anatomical size to humans, as well as genetic expression and development of high-risk atherosclerotic lesions which are similar to humans. Here we review the four models of porcine atherosclerosis, including the diabetic/hypercholesterolemic model, Rapacz-familial hypercholesterolemia pig, the (PCSK9) gain-of-function mutant pig model, and the Ossabaw miniature pig model of metabolic syndrome. All four models reliably represent features of human vascular disease. 1. Introduction Atherosclerosis is a systemic disease affecting virtually all vascular beds. Primary and secondary prevention strategies, novel pharmaceutical treatment modalities, and early intervention have reduced mortality rates of coronary artery disease. However, cardiovascular atherosclerotic diseases such as acute coronary syndromes, stroke, and aortic disease continue to be the leading cause of death in developed countries and the incidence is rapidly increasing in developing countries. Macrovascular disease is the major cause of death with patients suffering from diabetes mellitus (DM), both type I and type II, having a 2- to 6-fold greater risk of developing atherosclerosis compared to nondiabetic patients with comparable risk factors [1]. Type II diabetic patients often exhibit increased low density lipoprotein (LDL) and decreased high density lipoprotein (HDL) cholesterol levels and hypertension (i.e., the metabolic syndrome), as well as altered platelet function. Often the diagnosis of type II DM is made at the time the patient presents with coronary artery disease. Animal models have proven invaluable in understanding the pathophysiology of atherosclerosis as well as developing and testing treatment strategies. Genetically modified murine models have led to an understanding of the mechanisms of disease and the role of signaling pathways and genetic factors which play a major role in disease initiation and development. However, mice are limited by their varying lipid profiles, lack of spontaneous coronary artery disease, and development of disease in vascular beds which are in variance with human disease [2, 3]. DM has only a small effect on development of atherosclerosis in mice [4], and their small size limits
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