Spontaneous plaque rupture in mouse models of atherosclerosis is controversial, although numerous studies have discussed so-called “vulnerable plaque” phenotypes in mice. We compared the morphology and biomechanics of two acute and one chronic murine model of atherosclerosis to human coronaries of the thin-cap fibroatheroma (TCFA) phenotype. Our acute models were apolipoprotein E-deficient (ApoE−/−) and LDL receptor-deficient (LDLr−/−) mice, both fed a high-fat diet for 8 wk with simultaneous infusion of angiotensin II (ANG II), and our chronic mouse model was the apolipoprotein E-deficient strain fed a regular chow diet for 1 yr. We found that the mouse plaques from all three models exhibited significant morphological differences from human TCFA plaques, including the plaque burden, plaque thickness, eccentricity, and amount of the vessel wall covered by lesion as well as significant differences in the relative composition of plaques. These morphological differences suggested that the distribution of solid mechanical stresses in the walls may differ as well. Using a finite-element analysis computational solid mechanics model, we computed the relative distribution of stresses in the walls of murine and human plaques and found that although human TCFA plaques have the highest stresses in the thin fibrous cap, murine lesions do not have such stress distributions. Instead, local maxima of stresses were on the media and adventitia, away from the plaque. Our results suggest that if plaque rupture is possible in mice, it may be driven by a different mechanism than mechanics.

Objective: Although plaque erosion causes approximately 40% of all coronary thrombi and disproportionally affects women more than men, its mechanism is not well understood. The role of tissue mechanics in plaque rupture and regulation of mechanosensitive inflammatory proteins is well established, but their role in plaque erosion is unknown. Given obvious differences in morphology between plaque erosion and rupture, we hypothesized that inflammation in general as well as the association between local mechanical strain and inflammation known to exist in plaque rupture may not occur in plaque erosion. Therefore, our objective was to determine if similar mechanisms underlie plaque rupture and plaque erosion. Copyright: