Putative Murine Models of Plaque Rupture

Abstract

To be useful, animal models for human diseases must be well defined.1 Thus we are concerned that investigators will be mislead by the definitions and terminology used by Jackson et al1a to describe putative plaque rupture models in mice. We are especially concerned with their use of “acute plaque rupture” to describe murine lesions that do not mimic any of the key features of human plaque rupture and use of “buried fibrous caps” as questionable evidence for past ruptures. The consensus of cardiologists and pathologists is that rupture of human atherosclerotic lesions, defined as a structural defect in the fibrous cap overlying a necrotic core, is responsible for most coronary thrombi.2 This defect is associated with variable amounts of luminal thrombosis and plaque hemorrhage. Although neither thrombus nor plaque hemorrhage is required by this definition of plaque rupture,3 detection of these vital reactions is critically important to exclude possible post mortem artifacts. Confusingly, and in contrast to their original publications that emphasized luminal thrombosis,4,5 the current review by Jackson et al no longer considers thrombosis an important component of their “acute plaque rupture” model in mice. Interpretation of mouse models will be very confusing if terminology is used in an inconsistent fashion. Use of precise and transparent terms does not in any way limit the use of animal models to study specific processes. Death of smooth …