Molecular mechanisms of AGE/RAGE-mediated fibrosis in the diabetic heart

Figure 1 Rap1a in advanced glycation end product/the receptor for advanced glycation end product signaling. A potential role for Rap1a as a molecular switch mediating the AGE/RAGE signaling pathway in type 2 diabetes mellitus. Increased Rap1a activity may stimulate PKC-ζ to further promote matrix accumulation, RAGE expression and fibroblast differentiation to myofibroblasts. AGE: Advanced glycation end product; RAGE: The receptor for AGE; ECM: Extracellular matrix; cAMP: Cyclic AMP; GAP: GTPase-activating protein; PKC-ζ: The ζ isotype of protein kinase C; MAPK: Mitogen-activated protein kinase; ERK: Extracellular signal-regulated kinase.