Plaque rupture in humans and mice.
Despite the many studies of murine atherosclerosis, we do not yet know the relevance of the natural history of this model to the final events precipitated by plaque disruption of human atherosclerotic lesions. The literature has become particularly confused because of the common use of terms such as "instability", "vulnerable", "rupture", or even "thrombosis" for features of plaques in murine model systems not yet shown to rupture spontaneously and in an animal surprisingly resistant to formation of thrombi at sites of atherosclerosis. We suggest that use of conclusory terms like "vulnerable" and "stable" should be discouraged. Similarly, terms such as "buried fibrous caps" that imply preceding events that are unproven tend to create confusion. We will argue that such terminology may mislead readers by implying knowledge that does not yet exist. We suggest, instead, a focus on specific processes that various forms of data have implicated in plaque progression. For example, formation of the fibrous cap, protease activation, and cell death in the necrotic core can be well described and have all been modeled in well-defined experiments. The relevance of such well-defined, objective, descriptive observations in the mouse can be tested for relevance against data from human pathology.
Schwartz
Stephen M
SM
Department of Pathology, 815 Mercer Street, Room 421, University of Washington, Seattle, WA 98109-4714, USA. steves@u.washington.edu
Galis
Zorina S
ZS
Rosenfeld
Michael E
ME
Falk
Erling
E
D000818:Animals; D016477:Artifacts; D050197:Atherosclerosis / Q000503:physiopathology*; D006801:Humans; D051379:Mice; D010447:Peptide Hydrolases / Q000378:metabolism; D012422:Rupture, Spontaneous; D014973:Xanthomatosis / Q000503:physiopathology
D010447:Peptide Hydrolases