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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:714.)
© 2007 American Heart Association, Inc.

Brief Reviews

Assessment of Unstable Atherosclerosis in Mice

Christopher L. Jackson; Martin R. Bennett; Erik A.L. Biessen; Jason L. Johnson; Rob Krams

From the Bristol Heart Institute (C.L.J., J.L.J.), University of Bristol, UK; the University of Cambridge (M.R.B.), UK; the University of Leiden (E.A.L.B.), The Netherlands; and Laboratory of Physiology (R.K.), Free University Amsterdam, The Netherlands.

Correspondence to Christopher L. Jackson, Bristol Heart Institute, Level 7, Bristol Royal Infirmary, Bristol, UK. E-mail chris.jackson{at}bristol.ac.uk

There is an urgent need for representative animal models where prospective examination of the events leading up to plaque rupture and the rupture process itself can be performed. Recently, reports have begun to emerge that apolipoprotein E and low density lipoprotein receptor knockout mice may spontaneously develop unstable atherosclerosis, with plaques in certain parts of the arterial tree showing features suggestive of plaque rupture. Here we discuss the problems inherent in applying definitions of plaque rupture as seen in human arteries to mice; the anatomic locations in mice where unstable plaques do and do not occur; methods of inducing plaque instability in mice; and how to assess plaque stability in mice. These considerations lead us to a number of general recommendations.

There is an urgent need for representative animal models where prospective examination of the events leading up to plaque rupture and the rupture process itself can be performed. Recently, reports have begun to emerge that apolipoprotein E and low density lipoprotein receptor knockout mice may spontaneously develop unstable atherosclerosis, with plaques in certain parts of the arterial tree showing features suggestive of plaque rupture. Here we discuss the problems inherent in applying definitions of plaque rupture as seen in human arteries to mice; the anatomic locations in mice where unstable plaques do and do not occur; methods of inducing plaque instability in mice; and how to assess plaque stability in mice. These considerations lead us to a number of general recommendations.

Key Words: plaque rupture • animal models • apoE knockout mouse • vascular histopathology

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