Figure 7.

Proposed model for phenotypic modulation of VSMCs. Under LPS stimulation, the activation of IRAK4 promotes VSMCs phenotypic modulation from contractile type to synthetic type, which is characterized by markedly increased proliferation, migration, and secretion of inflammatory cytokine, MCP-1. MCP-1 can promote VSMCs migration and proliferation. NF-κB is a crucial regulatory factor of MCP-1 gene expression. IRAK4 is knockdown by siRNA and inhibited by IRAK1/4 inhibitor, which isaccompanied by the downregulation of NF-κB activity, phenotypic modulation from synthetic type to contractile type, and decrease in MCP-1 expression. These findings indicated that IL-1R-TLR participate inthe VSMCs phenotype modulation and downregulation of IRAK4, which inhibits LPS-mediated VSMCs dedifferentiation.