In collaboration with other researchers at Aarhus University, we have created three lines of gene-modified minipigs that develop atherosclerosis when fed a cholesterol-enriched diet: PCSK9 transgenic, APOE knockout and LDL receptor knockout pigs. The lines can be used to study atherosclerosis development in arteries with human-like dimensions and structure. They are particularly useful for research and development of atherosclerosis imaging techniques with clinical scanners. Similar to atherosclerosis in young and middle-aged humans, the early-to-moderate atherosclerosis that the pigs develop does not cause any symptoms.
Published in Al-Mashhadi et al. Sci Transl Med. 2013 and Shim et al. JACC Basic Transl 2018.
In collaboration with the Giehm Lab, we have developed a technique by which atherosclerosis can be induced in small animals by the injection of a recombinant adeno-associated virus encoding gain-of-function murine or human PCSK9. This is especially helpful for studies of atherosclerosis in gene-modified mouse lines. By circumventing the need to intercross such lines with APOE or LDL receptor knockout mice, it accelerates the pace of research and reduces the number of animals that need to be bred for atherosclerosis research. Plasmids needed for this technique are freely accessible through Addgene.org.