The role of PGE2 in atherosclerosis is complex, as it exhibits both pro-inflammatory and anti-inflammatory effects depending on cell types and PGE2 receptor subtypes, indicating a nuanced role for NOD2 in atherosclerosis.324 Intriguingly, a novel crosstalk between TLR4- and NOD2-mediated signaling was uncovered; NOD2 can sense the intensity of TLR4 signaling and modulate NF-κB pathway activation.325 This finding suggests that NOD2 serves as an immune initiator and functions as an immune regulator.326. This evidence concerns the gene TLR4 and atherosclerosis.