Abstract 553: Expression of TNFalfa and CCL18 is Increased as a Result of Cholesterol Accumulation in Macrophages
Innate immunity plays important role in atherogenesis. Immune reaction in artery wall involves both pro-and anti-inflammatory cytokines. We investigated cytokines’ mRNA expression in uninvolved and atherosclerotic human aortic intima. TNF-α and CCL18 were localized in autopsy aortic samples using immunohistochemistry. Expression of cytokine mRNA was measured by PCR or qPCR in the same samples. Primary culture of blood-derived monocytes/macrophages from healthy donors was used to study TNF-α and CCL18 mRNA expression induced by IFN-gamma and IL-4, respectively. Intracellular lipid accumulation was induced by incubation of cultured cells with atherogenic modified LDL isolated from blood of patients with documented coronary atherosclerosis. Immunohistochemistry demonstrated that the number of cytokine-positive cells (both TNF-α and CCL18) were increased in atherosclerotic lesions as compared with unaffected aortic intima. Cytokines were associated with different cell types including macrophages and non-macrophage cells. Both TNF-α and CCL18 were manly occurred in macrophages. Rice of both cytokines’ mRNA expression measured by PCR was observed in atherosclerotic lesion. In lipid-rich atherosclerotic lesion cytokine expression was the most considerable. Correlation between lipid content in aortic intima and cytokine expression was found. To elucidate the mechanism of elevation of lipid-associated cytokine expression, cell culture study was performed. Cultured monocytes/macrophages were incubated with atherogenic modified LDL of atherosclerotic patients and non-atherogenic LDL from healthy donors. In contrast to non-atherogenic LDL patients’ LDL induced intracellular cholesterol accumulation and increased mRNA expression of both TNF-α and CCL18 in cell culture. Thus, intracellular lipid accumulation caused by atherogenic modified LDL from atherosclerotic patients induces overexpression of TNFa and CCL18. This finding can explain the elevation of TNF-α and CCL18 expression in lipid-rich atherosclerotic lesions of human aorta.
- © 2013 by American Heart Association, Inc.