AGER and atherosclerosis: In vascular endothelial cells, S100 proteins binding to RAGE activates PI3K, ERK1/2 and JNK, ultimately leading to the activation of transcription factor Egr-1, which releases IL-6, CCL-2, vascular cell adhesion molecule-1 (VCAM-1) and ICAM-1, further inducing vascular dysfunction or atherosclerosis.