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Intracellular cholesterol crystals trigger an inflammatory response in macrophages by induction of NLRP3 inflammasomes. Typically, inflammation genes are induced by oxidized LDL. We hypothesized that extracellular cholesterol crystals, often present in atherosclerosis, can also trigger inflammatory responses in macrophages.
Murine RAW 264.7 macrophages were incubated with extracellular cholesterol crystals for 24 and 48 hr and gene activation was measured by quantitative PCR. Cholesterol complexed with methyl-β cyclodextrin (MCD) was used to introduce excess cholesterol into macrophages to evaluate the effect of intracellular cholesterol crystals. Four experiments were run for monocyte chemotactic protein (MCP-1) and three for tumor necrosis factor (TNF-α).
Extracellular cholesterol crystals induced a significant increase in transcription of MCP-1 (p<0.001). Cholesterol loading of macrophages with MCD had no effect (Figure). Extracellular cholesterol crystals significantly up-regulated TNF-α (p<0.01) while MCD+cholesterol was less effective (Figure).
Extracellular cholesterol crystals induce MCP-1 which recruits macrophages to sites of cholesterol crystal accumulation. This response is independent of cholesterol and crystal internalization, as demonstrated by lack of up-regulation of MCP-1 by MCD+cholesterol. This indicates that macrophages can be activated by cholesterol crystals in atherosclerotic lesions.
Moderated Poster Contributions
Poster Sessions, Expo North
Saturday, March 09, 2013, 3:45 p.m.-4:30 p.m.
Session Title: Acute Coronary Syndromes: Basic II
Abstract Category: 2. Acute Coronary Syndromes: Basic
Presentation Number: 1169M-177
- 2013 American College of Cardiology Foundation