Abstract 153: CCL22/ Macrophage-derived Chemokine Expression in the Setting of Atherosclerosis

Abstract

Introduction: CCL22 (macrophage-derived chemokine) is a member of the CC-family of chemokines. The functional role of CCL22 as a chemokine involves migration/ recruitment of monocytes and the stimulation of platelet activity. In this study, we investigated the relationship between CCL22 and atherosclerosis in monocytes/ macrophages of mice and humans with respect to atherosclerosis. Hypothesis: We assessed the hypothesis that CCL22 is involved in the process of atherosclerosis and can be a biological marker for progression of atherosclerosis and atherosclerotic disease. Methods: Apolipoprotein E deficient (apoE-/-) mice as atherosclerotic models were used for this study. Male apoE-/- mice were weaned at 8 weeks of age onto a high-cholesterol diet consisting of 1.25% cholesterol and were maintained on this diet for 12 weeks or 24 weeks. Another group of apoE-/- mice was maintained for 30 weeks on a normal chow diet. Serum CCL22 concentrations were measured by ELISA and expression of CCL22 mRNA in the atheroma were evaluated by real-time PCR. Furthermore immunohistochemical staining was performed. In vitro, the expressions of CCL22 in the mouse monocytes and macrophages were examined and discussed. The expression of CCL22 human monocytes/ macrophages and human atherosclerotic lesions were similarly investigated. Results: ApoE-/- mice had predominately high concentrations of CCL22 compared with wild-type (C57BL/6J) mice. ApoE-/- mice developed atherosclerotic lesions with aging and this was influenced by a high-cholesterol diet. CCL22 concentrations increased with aging and a high-cholesterol diet. Their atherosclerotic lesions, especially in macrophages contained abundant levels of CCL22. When the mouse monocyte differentiated into macrophage, the cells showed similar expression of CCL22. Similarly, human macrophages also expressed abundant levels of CCL22 more than monocytes. In addition, immunohistochemical analysis of human atherosclerotic lesions and coronary stenotic lesion revealed that macrophages express CCL22. Conclusion: In conclusion, these results suggested that this molecule is involved in the atherogenic processes and CCL22 may represent an attractive molecular marker for progression of atherosclerosis.