Hi Joseph

Difficult question to answer and depends on what aspect of AAA you are planning to investigate! Commonly, mice are employed for this due to small size, sequenced genome, genetically manipulated strains and availability of reagents (e.g. antibodies) to facilitate downstream analyses. I've attached a review on this for your reference

The ang-II infused apolipoprotein E deficient mouse is certainly the most widely used since it is naturally pro-atherosclerotic and incorporates key features including thrombosis (albeit intra-mural rather than intra-luminal), inflammation and male predilection for AAA formation. This can also be done in LDLR deficient mice, although our experience shows that the degree of AAA formation is significantly lower than the ApoE-/-. I guess a key difference between these mice and the human situation is the completely unrepresentative lipoprotein profile/metabolism of these mice (and in fact any mice)

^ sorry - hit submit by accident!!!

AAA can also be induced via peri-aortic application of calcium phosphate/calcium chloride. This is a fairly invasive procedure compared to ang-II infusion, however, benefits are that this can be applied to any mouse strain and indeed any organism you are interested in. AAAs formed in this way are within the infra-renal aorta compared to supra-renal in the ang-II infused models and therefore more closely matched to the clinical situation. However, the degree of thrombosis in this model is low - some people have suggested applying a second treatment of ferric chloride to start clotting, but I am unsure of the success of this approach.

Finally, infusion of the aorta with elastase can also be used to induce AAA. Personally I've not done this so can not comment with authority on the degree of success, although literature suggests that the degree of thrombosis is variable. As with the calcium phosphate model, AAA formation is not reliant on a specific genetic background and can therefore be applied to a range of mouse strains and other organisms.

Finally, there are a range of surgical approaches which have been used to mechanically manipulate the aorta to give an aneurysm-like bulge in the vascular wall but these seem less commonly used. They are detailed in the attached review.

Hope this helps!

Joe

Thanks Joe. An excellent answer and a great review. I have 2 related questions. 1. The mouse has recently received some criticism for studies of inflammation-mediated processes based upon genomic studies in mice and humans (Seok et al PNAS 2013 PMID 23401516). Is it known if the rat model better represents the inflammatory responses involved in human AAA development? 2. Topically applied elastase has been used to induce AAA formation in mice and rabbits. Is there a reason why this is not more commonly used? Has anyone tried this in a rat model?

Good questions Joseph, which I can't directly answer off the top of my head!

Regarding your first question, I have no doubt that there are significant discrepancies in the inflammatory mediators produced by mouse and human AAA. I'm working on revisions to a bioinformatics paper which shows little overlap in candidates secreted by mouse and human specimens. In terms of the rat, I've no direct experience in this, but colleagues working in the sepsis field utilise rats extensively - I'm guessing because of closer homology to the human situation than mice. Whether this translates in to rat AAA directly, I don't know.

Another issue (at least for our lab) with the rats is the lack of concomitant athero and resistance to ang-II induced AAA as this is the model we principally use, although I understand that an ApoE-/- rat may now be available.

Secondly RE elastase - I'm guessing that the reason for lack of use is that this is more technically demanding and time consuming which limits its ability to assess large sample sizes. The link here takes you to a Journal of Visual Experiments paper which details this neatly: http://www.jove.com/video/1280/creation-murine-experimental-abdominal-aortic-aneurysms-with?ID=1280

I've read about this working in pigs and other organisms, so I would be reasonably confident that it would be feasible in rats.

Hope that this helps

JOe

Thanks for the PNAS reference - is useful.