Porcine Models of Accelerated Coronary Atherosclerosis: Role of Diabetes Mellitus and Hypercholesterolemia

Abstract

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.

Development of Aortic Valve Disease in Familial Hypercholesterolemic Swine: Implications for Elucidating Disease Etiology

“…This absence of valvular calcification or stenosis in RFH swine was unlikely to be a result of insufficient animal age. RFH swine develop atherosclerosis on a similar developmental time frame as humans with HoFH (ie, by mid‐late adolescence for both of these groups41, 42); meanwhile, the adult age of the RFH swine studied herein is well past the porcine equivalent of the average age of CAVD diagnosis in humans with HoFH (17.9 years) 41. Limited histological examination of elderly RFH pigs (Figure S5) also did not show any progression of valvular pathology beyond what was present by 2 to 3 yo.…”

Role of Animal Models in Coronary Stenting

“…A diabetic phenotype can also be created by ablating the b cells of the pancreas with streptozotocin and providing an atherogenic diet. 22 More promising is the recent genetic manipulation of the Yucatan minipig, in which, by using DNA transposition and cloning by somatic cell nuclear transfer, animals are created with liverspecific expression of human D374Y-PCSK9, a gene responsible for severe hypercholesterolaemia and accelerated atherosclerosis. 22 Another genetic model is the Rapacz familial hypercholesterolemic pig, exhibit- ing elevated LDL levels and spontaneous atherosclerosis, due to a mutation in genes coding for apolipoproteins and LDL receptor.…”

“…22 Another genetic model is the Rapacz familial hypercholesterolemic pig, exhibit- ing elevated LDL levels and spontaneous atherosclerosis, due to a mutation in genes coding for apolipoproteins and LDL receptor. 22 The porcine model has other variants. An occluded coronary artery can be created by implanting a copper-coated stent.…”

Miniature optical coherence tomography-ultrasound probe for automatically coregistered three-dimensional intracoronary imaging with real-time display

“…We report the first demonstration of real-time three-dimensional (3-D) imaging and display of coregistered OCT-IVUS images in polar coordinates. The 3-D intracoronary imaging of familial hypercholesterolemic (FH) swine 13 is shown herein. Images of three major types of atherosclerotic plaques in human cadaver coronary segments further demonstrate the imaging capability of this novel probe.…”

“…FH swine is an ideal atherosclerotic animal model for intravascular imaging, 13 since lesions formed in FH swine closely mimic advanced human atherosclerosis. Human coronary arteries, which were up to 3 days postmortem and fixed with formalin, were also used for imaging.…”