P4HB and diabetes mellitus: SS induced by increased blood pressure non-specially activates the transmembrane proteins including RAGE, which can be specifically activated by AGEs induced by diabetes.1, 6, 44, 45 Either SS or AGEs promotes simultaneous proliferation and apoptosis, and both combinations have a synergistic effect (Supplementary Figure 3).1, 6 The VSMCs with strong co-expression of SM-α-actin and PDI are more prone to apoptosis, while VSMCs with a weak co-expression of SM-α-actin and PDI are more prone to proliferation.