Chronic unpredictable stress accelerates atherosclerosis through promoting inflammation in apolipoprotein E knockout mice.

INTRODUCTION

Chronic unpredictable stress (CUS) has been suggested to accelerate atherosclerosis. However, the underlying mechanism of this adverse effect is not fully understood. Since chronic stress can promote or even initiate inflammation response, which is thought to be a major contributor to atherogenesis, we postulated that stress-induced inflammatory response might be one important reason for CUS-promoted atherosclerotic disease.

MATERIALS AND METHODS

We used the CUS treated apolipoprotein E (ApoE)-deficient mice, which have been shown to spontaneously develop atherosclerosis with features similar to those seen in humans, as an animal model. Haematoxylin and eosin staining and immunohistostaining were used to analyze the plaque formation and composition.

RESULTS

Histological analysis clearly demonstrated that CUS treatment promoted the development of atherosclerotic lesions, such as triggering plaque rupture, increasing plaque size and plaque-to-surface ratio, and also led to profound changes in plaque composition, as evidenced by increased macrophage and T cell infiltration and decreased smooth muscle cell mass, all reflecting an unstable plaque phenotype. Moreover, adhesion molecular vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), acute phase reactant C-reactive protein (CRP), and proinflammatory cytokine interleukin-6 (IL-6) were significantly enhanced in CUS treated ApoE(-/-) mice compared with untreated control animals (P<0.01).

CONCLUSION

The involvement of CUS in the pathogenesis of atherosclerosis is at least partially attributable to its acceleration of inflammation.