Figure 1. Proposed modifications to preclinical pipeline for experimental atherosclerosis studies.

Prevention Studies may represent a good proof-of-principle for a novel therapeutic or gene knockout but in the setting of atherosclerosis may not translate to older patients with established disease (A). Instead, we should implement Intervention Studies, which we argue will better predict the effect of a therapeutic strategy for treating humans with advanced atherosclerotic lesions. Both of these approaches should analyze parameters that not only provide information about lesion size but also investigate multiple key cellular processes implicated in lesion vulnerability in humans (B). In addition, it is critical to identify innovative ways for validating results in preclinical animal studies to the extent possible including use of classic immunohistological analyses of human autopsy specimens as well as large-scale genomic approaches (C). Of course, the final validation of new CVD therapies will require well designed Clinical Trials (D).